|
1
|
Bomidi C, Sawyer FM, Shroyer N, Conner M, Estes MK, Blutt SE. Loss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection. J Virol 2025; 99:e0150724. [PMID: 39727412 PMCID: PMC11852729 DOI: 10.1128/jvi.01507-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024] Open
Abstract
Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi; however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, based on lack of shedding virus, despite the highly infectious nature of RV. This response was directly proportional to the extent of secretory cell deletion, with infection predominantly occurring in areas containing intact secretory cells. RV infection of Muc2 knockout mice recapitulated the secretory cell deletion phenotype, indicating that goblet cell loss is responsible for attenuated infection. Transcriptome analysis of Atoh1cKO intestine via single-cell RNA sequencing revealed downregulation of MHC II molecules specifically in tip enterocytes, and MHC II-/- mice were likewise resistant to RV infection. These data suggest a previously unknown role for both MUC2 and MHC II expression in susceptibility to RV infection.IMPORTANCERotavirus (RV) is a highly contagious pathogen that primarily infects mature intestinal enterocytes. Murine rotavirus readily infects infant and adult mice, enabling evaluation of RV infection and immunity. We report that mice lacking secretory cells are one of the few genetically modified mouse lines not susceptible to murine rotavirus. Further investigation revealed loss of mucin 2 (MUC2) expression or major histocompatibility complex II (MCH II) expression recapitulated this rare resistance to rotavirus infection, suggesting a previously unrecognized link between secretory cell products and major histocompatibility complex II expression. Furthermore, these mouse models provide a platform to investigate rotavirus pathogenesis.
Collapse
Affiliation(s)
- Carolyn Bomidi
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Faith M. Sawyer
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Noah Shroyer
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Margaret Conner
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Mary K. Estes
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Sarah E. Blutt
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| |
Collapse
|
|
2
|
Hakim MS, Gazali FM, Widyaningsih SA, Parvez MK. Driving forces of continuing evolution of rotaviruses. World J Virol 2024; 13:93774. [PMID: 38984077 PMCID: PMC11229848 DOI: 10.5501/wjv.v13.i2.93774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/06/2024] [Accepted: 05/17/2024] [Indexed: 06/24/2024] Open
Abstract
Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children (< 5 years). More than 90% of the global rotavirus infection in humans was caused by Rotavirus group A. Rotavirus infection has caused more than 200000 deaths annually and predominantly occurs in the low-income countries. Rotavirus evolution is indicated by the strain dynamics or the emergence of the unprecedented strain. The major factors that drive the rotavirus evolution include the genetic shift that is caused by the reassortment mechanism, either in the intra- or the inter-genogroup. However, other factors are also known to have an impact on rotavirus evolution. This review discusses the structure and types, epidemiology, and evolution of rotaviruses. This article also reviews other supplemental factors of rotavirus evolution, such as genetic reassortment, mutation rate, glycan specificity, vaccine introduction, the host immune responses, and antiviral drugs.
Collapse
Affiliation(s)
- Mohamad Saifudin Hakim
- Postgraduate School of Molecular Medicine, Erasmus MC-University Medical Center, Rotterdam 3015GD, Netherlands
- Viral Infection Working Group, International Society of Antimicrobial Chemotherapy, London EC4R 9AN, United Kingdom
| | - Faris Muhammad Gazali
- Master Program in Biotechnology, Postgraduate School, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Suci Ardini Widyaningsih
- Master of Medical Sciences in Clinical Investigation, Harvard Medical School, Boston, MA 02115, United States
| | - Mohammad Khalid Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
| |
Collapse
|
|
3
|
Carter MH, Gribble J, Diller JR, Denison MR, Mirza SA, Chappell JD, Halasa NB, Ogden KM. Human Rotaviruses of Multiple Genotypes Acquire Conserved VP4 Mutations during Serial Passage. Viruses 2024; 16:978. [PMID: 38932271 PMCID: PMC11209247 DOI: 10.3390/v16060978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/06/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Human rotaviruses exhibit limited tropism and replicate poorly in most cell lines. Attachment protein VP4 is a key rotavirus tropism determinant. Previous studies in which human rotaviruses were adapted to cultured cells identified mutations in VP4. However, most such studies were conducted using only a single human rotavirus genotype. In the current study, we serially passaged 50 human rotavirus clinical specimens representing five of the genotypes most frequently associated with severe human disease, each in triplicate, three to five times in primary monkey kidney cells then ten times in the MA104 monkey kidney cell line. From 13 of the 50 specimens, we obtained 25 rotavirus antigen-positive lineages representing all five genotypes, which tended to replicate more efficiently in MA104 cells at late versus early passage. We used Illumina next-generation sequencing and analysis to identify variants that arose during passage. In VP4, variants encoded 28 mutations that were conserved for all P[8] rotaviruses and 12 mutations that were conserved for all five genotypes. These findings suggest there may be a conserved mechanism of human rotavirus adaptation to MA104 cells. In the future, such a conserved adaptation mechanism could be exploited to study human rotavirus biology or efficiently manufacture vaccines.
Collapse
Affiliation(s)
- Maximilian H. Carter
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jennifer Gribble
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Julia R. Diller
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Mark R. Denison
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Sara A. Mirza
- Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
| | - James D. Chappell
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Natasha B. Halasa
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Kristen M. Ogden
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| |
Collapse
|
|
4
|
Donato CM, Handley A, Byars SG, Bogdanovic-Sakran N, Lyons EA, Watts E, Ong DS, Pavlic D, At Thobari J, Satria CD, Nirwati H, Soenarto Y, Bines JE. Vaccine Take of RV3-BB Rotavirus Vaccine Observed in Indonesian Infants Regardless of HBGA Status. J Infect Dis 2024; 229:1010-1018. [PMID: 37592804 PMCID: PMC11011179 DOI: 10.1093/infdis/jiad351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 08/19/2023] Open
Abstract
BACKGROUND Histo-blood group antigen (HBGA) status may affect vaccine efficacy due to rotavirus strains binding to HBGAs in a P genotype-dependent manner. This study aimed to determine if HBGA status affected vaccine take of the G3P[6] neonatal vaccine RV3-BB. METHODS DNA was extracted from stool samples collected in a subset (n = 164) of the RV3-BB phase IIb trial in Indonesian infants. FUT2 and FUT3 genes were amplified and sequenced, with any single-nucleotide polymorphisms analyzed to infer Lewis and secretor status. Measures of positive cumulative vaccine take were defined as serum immune response (immunoglobulin A or serum-neutralizing antibody) and/or stool excretion of RV3-BB virus. Participants were stratified by HBGA status and measures of vaccine take. RESULTS In 147 of 164 participants, Lewis and secretor phenotype were determined. Positive vaccine take was recorded for 144 (97.9%) of 147 participants with the combined phenotype determined. Cumulative vaccine take was not significantly associated with secretor status (relative risk, 1.00 [95% CI, .94-1.06]; P = .97) or Lewis phenotype (relative risk, 1.03 [95% CI, .94-1.14]; P = .33), nor was a difference observed when analyzed by each component of vaccine take. CONCLUSIONS The RV3-BB vaccine produced positive cumulative vaccine take, irrespective of HBGA status in Indonesian infants.
Collapse
Affiliation(s)
- Celeste M Donato
- Enteric Diseases Group, Murdoch Children's Research Institute
- Department of Paediatrics, The University of Melbourne, Parkville
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne
| | - Amanda Handley
- Enteric Diseases Group, Murdoch Children's Research Institute
- Medicines Development for Global Health, Southbank
| | - Sean G Byars
- Florey Institute of Neuroscience and Mental Health, Parkville, Australia
| | | | - Eleanor A Lyons
- Enteric Diseases Group, Murdoch Children's Research Institute
| | - Emma Watts
- Enteric Diseases Group, Murdoch Children's Research Institute
| | - Darren S Ong
- Enteric Diseases Group, Murdoch Children's Research Institute
| | - Daniel Pavlic
- Enteric Diseases Group, Murdoch Children's Research Institute
| | | | | | - Hera Nirwati
- Center for Child Health
- Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
| | - Yati Soenarto
- Center for Child Health
- Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr Sardjito Hospital, Yogyakarta, Indonesia
| | - Julie E Bines
- Enteric Diseases Group, Murdoch Children's Research Institute
- Department of Paediatrics, The University of Melbourne, Parkville
- Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Australia
| |
Collapse
|
|
5
|
Mansour Ghanaiee R, Fallah T, Karimi A, Sedighi I, Tariverdi M, Nazari T, Nahanmoghaddam N, Sedighi P, Nateghian A, Amirali A, Monavari SH, Fallahi M, Zahraei SM, Mahmoudi S, Elikaei A, Alebouyeh M. Multicenter Study of Rotavirus Infection, Diversity of Circulating Genotypes and Clinical Outcomes in Children ≤5 Years Old in Iran. Pediatr Infect Dis J 2024; 43:320-327. [PMID: 38190647 DOI: 10.1097/inf.0000000000004231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2024]
Abstract
BACKGROUND To determine the epidemiology of rotavirus group A (RVA) infection in symptomatic children, and analyze genotype diversity in association with clinical characteristics, geographical and seasonal changes. METHODS The stool samples of symptomatic children 5≥ years old were collected from 5 different hospitals during December 2020 and March 2022. Rotavirus stool antigen test was done and G and P genotypes of the positive samples were determined. Associations of the infection and genotype diversity with demographical and clinical data were assessed by statistical methods. RESULTS RVA infection was detected in 32.1% (300/934) of the patients (Ranges between 28.4% and 47.4%). An inverse association with age was detected, where the highest frequency was measured in children ≤12 months of age (175/482, 36.3%). The infection was more frequent during winter (124/284, 43.7%) and spring (64/187, 34.2%). Children who were exclusively fed with breast milk showed a lower rate of infection (72/251, 28.6%). Among the 46 characterized genotypes (17 single- and 29 mixed-genotype infections), G1P[8] and G9P[4] were more frequently detected in children <36 (67/234, 28.63%) and 36-60 (7/24, 29.16%) months of age children, respectively. A seasonal diversity in the circulating genotypes was detected in different cities. Children with G1P[8], G1P[6], and mixed-genotype infection experienced a shorter duration of hospitalization, and a higher frequency of nausea and severe diarrhea, respectively. CONCLUSIONS In this study high frequency of RVA infection was detected in symptomatic children in Iran. Moreover, genotype diversity according to geographic area, seasons, age groups, and clinical features of disease was detected.
Collapse
Affiliation(s)
- Roxana Mansour Ghanaiee
- From the Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tina Fallah
- Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Abdollah Karimi
- From the Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Iraj Sedighi
- Department of Pediatrics, Faculty of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Marjan Tariverdi
- Department of Pediatrics, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Tayebe Nazari
- From the Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Negin Nahanmoghaddam
- Department of Pediatrics, Bouali Hospital Children's Hospital, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Parinaz Sedighi
- Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
- Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Alireza Nateghian
- Department of Pediatrics, Ali Asghar Children's hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Arezu Amirali
- From the Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Seyed Hamidreza Monavari
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahsa Fallahi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Seyed Mohsen Zahraei
- Center for Communicable Diseases Control, Ministry of Health and Medical Education, Tehran, Iran
| | - Sussan Mahmoudi
- Center for Communicable Diseases Control, Ministry of Health and Medical Education, Tehran, Iran
| | - Ameneh Elikaei
- Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Masoud Alebouyeh
- From the Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
6
|
Carossino M, Vissani MA, Barrandeguy ME, Balasuriya UBR, Parreño V. Equine Rotavirus A under the One Health Lens: Potential Impacts on Public Health. Viruses 2024; 16:130. [PMID: 38257830 PMCID: PMC10819593 DOI: 10.3390/v16010130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 12/29/2023] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Group A rotaviruses are a well-known cause of viral gastroenteritis in infants and children, as well as in many mammalian species and birds, affecting them at a young age. This group of viruses has a double-stranded, segmented RNA genome with high genetic diversity linked to point mutations, recombination, and, importantly, reassortment. While initial molecular investigations undertaken in the 1900s suggested host range restriction among group A rotaviruses based on the fact that different gene segments were distributed among different animal species, recent molecular surveillance and genome constellation genotyping studies conducted by the Rotavirus Classification Working Group (RCWG) have shown that animal rotaviruses serve as a source of diversification of human rotavirus A, highlighting their zoonotic potential. Rotaviruses occurring in various animal species have been linked with contributing genetic material to human rotaviruses, including horses, with the most recent identification of equine-like G3 rotavirus A infecting children. The goal of this article is to review relevant information related to rotavirus structure/genomic organization, epidemiology (with a focus on human and equine rotavirus A), evolution, inter-species transmission, and the potential zoonotic role of equine and other animal rotaviruses. Diagnostics, surveillance and the current status of human and livestock vaccines against RVA are also reviewed.
Collapse
Affiliation(s)
- Mariano Carossino
- Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA;
- Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Maria Aldana Vissani
- Escuela de Veterinaria, Facultad de Ciencias Agrarias y Veterinarias, Universidad del Salvador, Pilar, Buenos Aires B1630AHU, Argentina; (M.A.V.); (M.E.B.)
- Instituto de Virología, CICVyA, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires B1686LQF, Argentina;
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1033AAJ, Argentina
| | - Maria E. Barrandeguy
- Escuela de Veterinaria, Facultad de Ciencias Agrarias y Veterinarias, Universidad del Salvador, Pilar, Buenos Aires B1630AHU, Argentina; (M.A.V.); (M.E.B.)
- Instituto de Virología, CICVyA, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires B1686LQF, Argentina;
| | - Udeni B. R. Balasuriya
- Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA;
- Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Viviana Parreño
- Instituto de Virología, CICVyA, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires B1686LQF, Argentina;
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1033AAJ, Argentina
| |
Collapse
|
|
7
|
Poddar S, Roy R, Kar P. Elucidating the conformational dynamics of histo-blood group antigens and their interactions with the rotavirus spike protein through computational lens. J Biomol Struct Dyn 2023; 42:13201-13215. [PMID: 37909470 DOI: 10.1080/07391102.2023.2274979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/18/2023] [Indexed: 11/03/2023]
Abstract
In the present study, we investigated the conformational dynamics of histo-blood group antigens (HBGAs) and their interactions with the VP8* domain of four rotavirus genotypes (P[4], P[6], P[19], and P[11]) utilizing all-atom molecular dynamics simulations in explicit water. Our study revealed distinct changes in the dynamic behavior of the same glycan due to linkage variations. We observed that LNFPI HBGA having a terminal β linkage shows two dominant conformations after complexation, whereas only one was obtained for LNFPI with a terminal α linkage. Interestingly, both variants displayed a single dominant structure in the free state. Similarly, LNT and LNnT show a shift in their dihedral linkage profile between their two terminal monosaccharides because of a change in the linkage from β(1-3) to β(1-4). The molecular mechanics generalized Born surface area (MM/GBSA) calculations yielded the highest binding affinity for LNFPI(β)/P[6] (-13.93 kcal/mol) due to the formation of numerous hydrogen bonds between VP8* and HBGAs. LNnT binds more strongly to P[11] (-12.88 kcal/mol) than LNT (-4.41 kcal/mol), suggesting a single change in the glycan linkage might impact its binding profile significantly. We have also identified critical amino acids and monosaccharides (Gal and GlcNAc) that contributed significantly to the protein-ligand binding through the per-residue decomposition of binding free energy. Moreover, we found that the interaction between the same glycan and different protein receptors within the same rotavirus genogroup influenced the micro-level dynamics of the glycan. Overall, our study helps a deeper understanding of the H-type HBGA and rotavirus spike protein interaction.Communicated by Ramaswamy H. Sarma.
Collapse
Affiliation(s)
- Sayan Poddar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Rajarshi Roy
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Parimal Kar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| |
Collapse
|
|
8
|
Kim JS, Jeong HW, Park SH, Kim JA, Jin YH, Kim HS, Jung S, Lee JI, Lee JH. Genotypic shift in rotavirus associated with neonatal outbreaks in Seoul, Korea. J Clin Virol 2023; 164:105497. [PMID: 37253299 DOI: 10.1016/j.jcv.2023.105497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 05/22/2023] [Accepted: 05/24/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND Rotavirus group A (RVA) is a causative agent of acute gastroenteritis among young children worldwide, despite the global expansion of rotavirus vaccination. In Korea, although the prevalence of RVA has been reduced among young children owing to vaccination, nosocomial infections still occur among neonates. OBJECTIVES The aim of this study was to investigate the molecular epidemiology of RVA strains associated with several neonatal outbreaks in Seoul from 2017 to 2020. STUDY DESIGN Clinical and environmental samples were collected and screened for the presence of RVA using ELISA and PCR targeting VP6, respectively. RVA-positive strains were genotyped via RT-PCR and subsequent sequencing of VP4 and VP7 and were phylogenetically compared with RVA strains from other countries. RESULTS During 2017-2020, a total of 15 RVA outbreaks occurred at neonatal facilities (six in hospital neonatal wards and nine in postpartum care centers) in Seoul, and only two RVA genotypes were detected: G4P[6] and G8P[6]. G8P[6] emerged in Seoul November 2018 and immediately became the predominant genotype among neonates, at least up to 2020. Phylogenetic analysis revealed that the G8P[6] genotype in this study was closely related to G8P[6] strains first identified in Korea in 2017, but differed from G8P[6] strains detected in Africa. CONCLUSIONS A novel G8P[6] genotype of RVA strains has emerged and caused outbreaks among neonates in Seoul. Continued surveillance for circulating RVA genotypes is imperative to monitor genotype changes and their potential risks to public health.
Collapse
Affiliation(s)
- Jin Seok Kim
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea.
| | - Hyo-Won Jeong
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| | - Sook Hyun Park
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| | - Jin-Ah Kim
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| | - Young Hee Jin
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| | - Hyun Soo Kim
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, Republic of Korea
| | - Soyoung Jung
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| | - Jae In Lee
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| | - Jib-Ho Lee
- Emerging Infectious Diseases Team, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gyeonggi-do, Republic of Korea
| |
Collapse
|
|
9
|
Chioma Mgbodile F, Nwagu TNT. Probiotic therapy, African fermented foods and food-derived bioactive peptides in the management of SARS-CoV-2 cases and other viral infections. BIOTECHNOLOGY REPORTS 2023; 38:e00795. [PMID: 37041970 PMCID: PMC10066861 DOI: 10.1016/j.btre.2023.e00795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 03/20/2023] [Accepted: 03/27/2023] [Indexed: 04/04/2023]
Abstract
The current paper focuses on the impact of probiotics, African fermented foods and bioactive peptides on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity and related viral infections. Using probiotics or bioactive peptides as therapeutic adjuncts appears superior to standard care alone. Probiotics play critical roles in innate and adaptive immune modulation by balancing the gut microbiota to combat viral infections, secondary bacterial infections and microbial dysbiosis. African fermented foods contain abundant potential probiotic microorganisms such as the lactic acid bacteria (LAB), Saccharomyces, and Bacillus. More so, fermented food-derived bioactive peptides play vital roles in preventing cardiovascular diseases, hypertension, lung injury, diabetes, and other COVID-19 comorbidities. Regularly incorporating potential probiotics and bioactive peptides into diets should enable a build-up of the benefits in the body system that may result in a better prognosis, especially in COVID-19 patients with underlying complexities. Despite the reported therapeutic potentials of probiotics and fermented foods, numerous setbacks exist regarding their application in disease management. These shortfalls underscore an evident need for more studies to evaluate the specific potentials of probiotics and traditional fermented foods in ameliorating SARS-CoV-2 and other viral infections.
Collapse
|
|
10
|
Anglenius H, Mäkivuokko H, Ahonen I, Forssten SD, Wacklin P, Mättö J, Lahtinen S, Lehtoranta L, Ouwehand AC. In Vitro Screen of Lactobacilli Strains for Gastrointestinal and Vaginal Benefits. Microorganisms 2023; 11:microorganisms11020329. [PMID: 36838294 PMCID: PMC9967617 DOI: 10.3390/microorganisms11020329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/21/2023] [Accepted: 01/23/2023] [Indexed: 01/31/2023] Open
Abstract
Traditional probiotics comprise mainly lactic acid bacteria that are safe for human use, tolerate acid and bile, and adhere to the epithelial lining and mucosal surfaces. In this study, one hundred commercial and non-commercial strains that were isolated from human feces or vaginal samples were tested with regards to overall growth in culture media, tolerance to acid and bile, hydrogen peroxide (H2O2) production, and adhesion to vaginal epithelial cells (VECs) and to blood group antigens. As a result, various of the tested lactobacilli strains were determined to be suitable for gastrointestinal or vaginal applications. Commercial strains grew better than the newly isolated strains, but tolerance to acid was a common property among all tested strains. Tolerance to bile varied considerably between the strains. Resistance to bile and acid correlated well, as did VEC adhesion and H2O2 production, but H2O2 production was not associated with resistance to bile or acid. Except for L. iners strains, vaginal isolates had better overall VEC adhesion and higher H2O2 production. Species- and strain-specific differences were evident for all parameters. Rank-ordered clustering with nine clusters was used to identify strains that were suitable for gastrointestinal or vaginal health, demonstrating that the categorization of strains for targeted health indications is possible based on the parameters that were measured in this study.
Collapse
Affiliation(s)
- Heli Anglenius
- IFF Health and Biosciences, 02460 Kantvik, Finland
- Correspondence:
| | | | | | | | | | - Jaana Mättö
- Finnish Red Cross Blood Service, 00310 Helsinki, Finland
| | | | | | | |
Collapse
|
|
11
|
Desselberger U. 14th International dsRNA Virus Symposium, Banff, Alberta, Canada, 10-14 October 2022. Virus Res 2023; 324:199032. [PMID: 36584760 PMCID: PMC10242350 DOI: 10.1016/j.virusres.2022.199032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/23/2022] [Accepted: 12/24/2022] [Indexed: 12/29/2022]
Abstract
This triennial International dsRNA Virus Symposium covered original data which have accrued during the most recent five years. In detail, the genomic diversity of these viruses continued to be explored; various structure-function studies were carried out using reverse genetics and biophysical techniques; intestinal organoids proved to be very suitable for special pathogenesis studies; and the potential of next generation rotavirus vaccines including use of rotavirus recombinants as vectored vaccine candidates was explored. 'Non-lytic release of enteric viruses in cloaked vesicles' was the topic of the keynote lecture by Nihal Altan-Bonnet, NIH, Bethesda, USA. The Jean Cohen lecturer of this meeting was Polly Roy, London School of Hygiene and Tropical Medicine, who spoke on aspects of the replication cycle of bluetongue viruses, and how some of the data are similar to details of rotavirus replication.
Collapse
Affiliation(s)
- Ulrich Desselberger
- Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, U.K..
| |
Collapse
|
|
12
|
Raev S, Amimo J, Saif L, Vlasova A. Intestinal mucin-type O-glycans: the major players in the host-bacteria-rotavirus interactions. Gut Microbes 2023; 15:2197833. [PMID: 37020288 PMCID: PMC10078158 DOI: 10.1080/19490976.2023.2197833] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/28/2023] [Indexed: 04/07/2023] Open
Abstract
Rotavirus (RV) causes severe diarrhea in young children and animals worldwide. Several glycans terminating in sialic acids (SAs) and histo-blood group antigens (HBGAs) on intestinal epithelial cell (IEC) surface have been recognized to act as attachment sites for RV. IECs are protected by the double layer of mucus of which O-glycans (including HBGAs and SAs) are a major organic component. Luminal mucins, as well as bacterial glycans, can act as decoy molecules removing RV particles from the gut. The composition of the intestinal mucus is regulated by complex O-glycan-specific interactions among the gut microbiota, RV and the host. In this review, we highlight O-glycan-mediated interactions within the intestinal lumen prior to RV attachment to IECs. A better understanding of the role of mucus is essential for the development of alternative therapeutic tools including the use of pre- and probiotics to control RV infection.
Collapse
Affiliation(s)
- S.A. Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
| | - J.O. Amimo
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
- Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya
| | - L.J. Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
| | - A.N. Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USA
| |
Collapse
|
|
13
|
Farahmand M, Latifi T, Kachooei A, Jalilvand S, Shoja Z. Circulating rotavirus P[8]-lineage IV, unlike P[8]-lineage III, significantly related to nonsecretors status in Iranian children. J Med Virol 2023; 95:e28160. [PMID: 36123611 DOI: 10.1002/jmv.28160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/20/2022] [Accepted: 09/14/2022] [Indexed: 01/11/2023]
Abstract
Rotavirus (RV) P[8] strains are responsible for the most of the RV infections globally and are significantly associated with the secretor and Lewis positive status. Among the distinct P[8] lineages, different ligand affinities have been detected which can be linked to differences in secretor status associated histo-blood group antigens (HBGAs). Herein, we report the lineages of P[8] strains and their associated secretor and Lewis antigen phenotypes in Iranian children. The phylogenetic tree and sequence analyses showed that the most common detected RV P[8] strain belonged to P[8]-lineage III (92%) and were significantly associated with secretor and Lewis positive status. In contrast, 8% of P[8] strains clustered into the P[8]-lineage IV and were significantly associated with nonsecretor status, implying that lineage IV tends to infect nonsecretor individuals. Furthermore, protein modeling and amino acid analyses of the VP8* glycan binding site of Iranian P[8]-lineage IV strains indicated two residual substitutions (T184V and N216V/I) compared to the P[8]-lineage III strains that might have affected the glycan affinity among P[8]-lineages IV strains. The corresponding residual changes might permit their continued transmission in nonsecretor children in competition with other P[8]-lineages. Although nonsecretors show natural resistant to P[8] strains, but such residual changes might overcome this natural resistance which in turn might indirectly contribute to the decline in the vaccine efficacy in populations where HBGA polymorphism allows their circulation at high frequency.
Collapse
Affiliation(s)
- Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Tayebeh Latifi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Atefeh Kachooei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Somayeh Jalilvand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Zabihollah Shoja
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran.,Research Center for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| |
Collapse
|
|
14
|
Maass T, Ssebyatika G, Brückner M, Breckwoldt L, Krey T, Mallagaray A, Peters T, Frank M, Creutznacher R. Binding of Glycans to the SARS CoV-2 Spike Protein, an Open Question: NMR Data on Binding Site Localization, Affinity, and Selectivity. Chemistry 2022; 28:e202202614. [PMID: 36161798 PMCID: PMC9537997 DOI: 10.1002/chem.202202614] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/26/2022] [Accepted: 09/26/2022] [Indexed: 11/25/2022]
Abstract
We have used NMR experiments to explore the binding of selected glycans and glycomimetics to the SARS CoV-2 spike glycoprotein (S-protein) and to its receptor binding domain (RBD). STD NMR experiments confirm the binding of sialoglycans to the S-protein of the prototypic Wuhan strain virus and yield dissociation constants in the millimolar range. The absence of STD effects for sialoglycans in the presence of the Omicron/BA.1 S-protein reflects a loss of binding as a result of S-protein evolution. Likewise, no STD effects are observed for the deletion mutant Δ143-145 of the Wuhan S-protein, thus supporting localization of the binding site in the N-terminal domain (NTD). The glycomimetics Oseltamivir and Zanamivir bind weakly to the S-protein of both virus strains. Binding of blood group antigens to the Wuhan S-protein cannot be confirmed by STD NMR. Using 1 H,15 N TROSY HSQC-based chemical shift perturbation (CSP) experiments, we excluded binding of any of the ligands studied to the RBD of the Wuhan S-protein. Our results put reported data on glycan binding into perspective and shed new light on the potential role of glycan-binding to the S-protein.
Collapse
Affiliation(s)
- Thorben Maass
- University of Lübeck: Universitat zu LubeckInstitute of Chemistry and MetabolomicsGERMANY
| | - George Ssebyatika
- University of Lübeck: Universitat zu LubeckInstitute of BiochemistryGERMANY
| | - Marlene Brückner
- University of Lübeck: Universitat zu LubeckInstitute of Chemistry and MetabolomicsGERMANY
| | - Lea Breckwoldt
- University of Lübeck: Universitat zu LubeckInstitute of Chemistry and MetabolomicsGERMANY
| | - Thomas Krey
- University of Lübeck: Universitat zu LubeckInstitute of BiochemistryGERMANY
| | - Alvaro Mallagaray
- University of Lübeck: Universitat zu LubeckInstitute of Chemistry and MetabolomicsGERMANY
| | - Thomas Peters
- Institute for Chemistry and MetabolomicsUniversität zu LübeckRatzeburger Allee 16023562LübeckGERMANY
| | | | - Robert Creutznacher
- University of Lübeck: Universitat zu LubeckInstitute of Chemistry and MetabolomicsGERMANY
| |
Collapse
|
|
15
|
Lalithamaheswari B, Anu Radha C. Structural and conformational dynamics of human milk oligosaccharides, lacto- N-fucopentaose I and II, through molecular dynamics simulation. J Carbohydr Chem 2022. [DOI: 10.1080/07328303.2022.2150203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- B. Lalithamaheswari
- Research Laboratory of Molecular Biophysics, Department of Physics, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - C. Anu Radha
- Research Laboratory of Molecular Biophysics, Department of Physics, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| |
Collapse
|
|
16
|
Gutierrez MB, de Assis RMS, Arantes I, Fumian TM. Full genotype constellations analysis of unusual DS-1-like G12P[6] and G6P[8] rotavirus strains detected in Brazil, 2019. Virology 2022; 577:74-83. [PMID: 36323046 DOI: 10.1016/j.virol.2022.10.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 10/20/2022] [Accepted: 10/21/2022] [Indexed: 11/07/2022]
Abstract
Rotavirus A (RVA) is a major cause of acute gastroenteritis (AGE) in children worldwide. We report unusual RVA G12P[6] and G6P[8] strains isolated from fecal samples from Brazilian children hospitalized for AGE. The characterized RVA have genome segments backbone: G12-P[6]/ G6-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 of DS-1-like genogroup. Our study describes the first identification of G6P[8], a DS-1-like genogroup strain. Nucleotide analysis of VP7 and VP4 genes revealed that all G12 Brazilian strains clustered into the sub-lineages IIIB, mostly associated with P[6] lineage I. Additionally, our G6 lineage I strains were closely related to German G6 genotypes, bound with P[8] lineage III, differing from both vaccine strains. The comparative sequence analysis of our strains with vaccine strains revealed amino acid substitutions located in immunodominant regions of VP7 and VP4 proteins. Continuous monitoring of RVA genotypes is essential to evaluate the impact of vaccination on the dynamic nature of RVA evolution.
Collapse
Affiliation(s)
- Meylin Bautista Gutierrez
- Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Av. Brasil, 4365, Rio de Janeiro, RJ 21040-360, Brazil
| | - Rosane Maria Santos de Assis
- Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Av. Brasil, 4365, Rio de Janeiro, RJ 21040-360, Brazil
| | - Ighor Arantes
- Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Av. Brasil, 4365, Rio de Janeiro, RJ 21040-360, Brazil
| | - Tulio Machado Fumian
- Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Av. Brasil, 4365, Rio de Janeiro, RJ 21040-360, Brazil.
| |
Collapse
|
|
17
|
Raev SA, Omwando AM, Guo Y, Raque MS, Amimo JO, Saif LJ, Vlasova AN. Glycan-mediated interactions between bacteria, rotavirus and the host cells provide an additional mechanism of antiviral defence. Benef Microbes 2022; 13:383-396. [PMID: 36239669 DOI: 10.3920/bm2022.0026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Limited efficacy of rotavirus (RV) vaccines in children in developing countries and in animals remains a significant problem necessitating further search for additional approaches to control RV-associated gastroenteritis. During cell attachment and entry events, RV interacts with cell surface O-glycans including histo-blood group antigens (HBGAs). Besides modulation of the protective immunity against RV, several commensal and probiotic bacteria were shown to express HBGA-like substances suggesting that they may affect RV attachment and entry into the host cells. Moreover, some beneficial bacteria have been shown to possess the ability to bind host HBGAs via sugar specific proteins called lectins. However, limited research has been done to evaluate the effects of HBGA-expressing and/or HBGA-binding bacteria on RV infection. The aim of this study was to investigate the ability of selected commensal and probiotic bacteria to bind different RV strains via HBGAs and to block RV infection of IPEC-J2 cells. Our data indicated that Gram-negative probiotic Escherichia coli Nissle 1917 (E. coli Nissle 1917) and commensal Gram-positive (Streptococcus bovis and Bifidobacterium adolescentis) and Gram-negative (Bacteroides thetaiotaomicron, Clostridium clostridioforme and Escherichia coli G58 (E. coli G58) bacteria of swine origin expressed HBGAs which correlated with their ability to bind group A and C RVs. Additionally, Gram-positive E. coli 1917 and E. coli G58 demonstrated the ability to block RV attachment onto IPEC-J2 cells. Taken together, our results support the hypothesis that physical interactions between RVs and HBGA-expressing beneficial bacteria may limit RV replication.
Collapse
Affiliation(s)
- S A Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - A M Omwando
- Department of Public Health, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Nairobi, P.O. Box 29053, 00625 Nairobi, Kenya
| | - Y Guo
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - M S Raque
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - J O Amimo
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, P.O. Box 29053, 00625 Nairobi, Kenya
| | - L J Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| | - A N Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
| |
Collapse
|
|
18
|
Moya-Gonzálvez EM, Peña-Gil N, Rubio-del-Campo A, Coll-Marqués JM, Gozalbo-Rovira R, Monedero V, Rodríguez-Díaz J, Yebra MJ. Infant Gut Microbial Metagenome Mining of α-l-Fucosidases with Activity on Fucosylated Human Milk Oligosaccharides and Glycoconjugates. Microbiol Spectr 2022; 10:e0177522. [PMID: 35943155 PMCID: PMC9430343 DOI: 10.1128/spectrum.01775-22] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/01/2022] [Indexed: 11/21/2022] Open
Abstract
The gastrointestinal microbiota members produce α-l-fucosidases that play key roles in mucosal, human milk, and dietary oligosaccharide assimilation. Here, 36 open reading frames (ORFs) coding for putative α-l-fucosidases belonging to glycosyl hydrolase family 29 (GH29) were identified through metagenome analysis of breast-fed infant fecal microbiome. Twenty-two of those ORFs showed a complete coding sequence with deduced amino acid sequences displaying the highest degree of identity with α-l-fucosidases from Bacteroides thetaiotaomicron, Bacteroides caccae, Phocaeicola vulgatus, Phocaeicola dorei, Ruminococcus gnavus, and Streptococcus parasanguinis. Based on sequence homology, 10 α-l-fucosidase genes were selected for substrate specificity characterization. The α-l-fucosidases Fuc18, Fuc19A, Fuc35B, Fuc39, and Fuc1584 showed hydrolytic activity on α1,3/4-linked fucose present in Lewis blood antigens and the human milk oligosaccharide (HMO) 3-fucosyllactose. In addition, Fuc1584 also hydrolyzed fucosyl-α-1,6-N-acetylglucosamine (6FN), a component of the core fucosylation of N-glycans. Fuc35A and Fuc193 showed activity on α1,2/3/4/6 linkages from H type-2, Lewis blood antigens, HMOs and 6FN. Fuc30 displayed activity only on α1,6-linked l-fucose, and Fuc5372 showed a preference for α1,2 linkages. Fuc2358 exhibited a broad substrate specificity releasing l-fucose from all the tested free histo-blood group antigens, HMOs, and 6FN. This latest enzyme also displayed activity in glycoconjugates carrying lacto-N-fucopentaose II (Lea) and lacto-N-fucopentaose III (Lex) and in the glycoprotein mucin. Fuc18, Fuc19A, and Fuc39 also removed l-fucose from neoglycoproteins and human α-1 acid glycoprotein. These results give insight into the great diversity of α-l-fucosidases from the infant gut microbiota, thus supporting the hypothesis that fucosylated glycans are crucial for shaping the newborn microbiota composition. IMPORTANCE α-l-Fucosyl residues are frequently present in many relevant glycans, such as human milk oligosaccharides (HMOs), histo-blood group antigens (HBGAs), and epitopes on cell surface glycoconjugate receptors. These fucosylated glycans are involved in a number of mammalian physiological processes, including adhesion of pathogens and immune responses. The modulation of l-fucose content in such processes may provide new insights and knowledge regarding molecular interactions and may help to devise new therapeutic strategies. Microbial α-l-fucosidases are exoglycosidases that remove α-l-fucosyl residues from free oligosaccharides and glycoconjugates and can be also used in transglycosylation reactions to synthesize oligosaccharides. In this work, α-l-fucosidases from the GH29 family were identified and characterized from the metagenome of fecal samples of breastfed infants. These enzymes showed different substrate specificities toward HMOs, HBGAs, naturally occurring glycoproteins, and neoglycoproteins. These novel glycosidase enzymes from the breast-fed infant gut microbiota, which resulted in a good source of α-l-fucosidases, have great biotechnological potential.
Collapse
Affiliation(s)
- Eva M. Moya-Gonzálvez
- Laboratorio de Bacterias Lácticas y Probióticos, Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Valencia, Spain
| | - Nazaret Peña-Gil
- Departamento de Microbiología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
- INCLIVA, Instituto de Investigación Sanitaría del Hospital Clínico de Valencia, Valencia, Spain
| | - Antonio Rubio-del-Campo
- Laboratorio de Bacterias Lácticas y Probióticos, Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Valencia, Spain
| | - José M. Coll-Marqués
- Laboratorio de Bacterias Lácticas y Probióticos, Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Valencia, Spain
| | - Roberto Gozalbo-Rovira
- Departamento de Microbiología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
- INCLIVA, Instituto de Investigación Sanitaría del Hospital Clínico de Valencia, Valencia, Spain
| | - Vicente Monedero
- Laboratorio de Bacterias Lácticas y Probióticos, Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Valencia, Spain
| | - Jesús Rodríguez-Díaz
- Departamento de Microbiología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
- INCLIVA, Instituto de Investigación Sanitaría del Hospital Clínico de Valencia, Valencia, Spain
| | - María J. Yebra
- Laboratorio de Bacterias Lácticas y Probióticos, Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Valencia, Spain
| |
Collapse
|
|
19
|
Guo Y, Raev S, Kick MK, Raque M, Saif LJ, Vlasova AN. Rotavirus C Replication in Porcine Intestinal Enteroids Reveals Roles for Cellular Cholesterol and Sialic Acids. Viruses 2022; 14:v14081825. [PMID: 36016447 PMCID: PMC9416568 DOI: 10.3390/v14081825] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/14/2022] [Accepted: 08/16/2022] [Indexed: 11/25/2022] Open
Abstract
Rotaviruses (RVs) are a significant cause of severe diarrheal illness in infants and young animals, including pigs. Group C rotavirus (RVC) is an emerging pathogen increasingly reported in pigs and humans worldwide, and is currently recognized as the major cause of gastroenteritis in neonatal piglets that results in substantial economic losses to the pork industry. However, little is known about RVC pathogenesis due to the lack of a robust cell culture system, with the exception of the RVC Cowden strain. Here, we evaluated the permissiveness of porcine crypt-derived 3D and 2D intestinal enteroid (PIE) culture systems for RVC infection. Differentiated 3D and 2D PIEs were infected with porcine RVC (PRVC) Cowden G1P[1], PRVC104 G3P[18], and PRVC143 G6P[5] virulent strains, and the virus replication was measured by qRT-PCR. Our results demonstrated that all RVC strains replicated in 2D-PIEs poorly, while 3D-PIEs supported a higher level of replication, suggesting that RVC selectively infects terminally differentiated enterocytes, which were less abundant in the 2D vs. 3D PIE cultures. While cellular receptors for RVC are unknown, target cell surface carbohydrates, including histo-blood-group antigens (HBGAs) and sialic acids (SAs), are believed to play a role in cell attachment/entry. The evaluation of the selective binding of RVCs to different HBGAs revealed that PRVC Cowden G1P[1] replicated to the highest titers in the HBGA-A PIEs, while PRVC104 or PRVC143 achieved the highest titers in the HBGA-H PIEs. Further, contrasting outcomes were observed following sialidase treatment (resulting in terminal SA removal), which significantly enhanced Cowden and RVC143 replication, but inhibited the growth of PRVC104. These observations suggest that different RVC strains may recognize terminal (PRVC104) as well as internal (Cowden and RVC143) SAs on gangliosides. Finally, several cell culture additives, such as diethylaminoethyl (DEAE)-dextran, cholesterol, and bile extract, were tested to establish if they could enhance RVC replication. We observed that only DEAE-dextran significantly enhanced RVC attachment, but it had no effect on RVC replication. Additionally, the depletion of cellular cholesterol by MβCD inhibited Cowden replication, while the restoration of the cellular cholesterol partially reversed the MβCD effects. These results suggest that cellular cholesterol plays an important role in the replication of the PRVC strain tested. Overall, our study has established a novel robust and physiologically relevant system to investigate RVC pathogenesis. We also generated novel, experimentally derived evidence regarding the role of host glycans, DEAE, and cholesterol in RVC replication, which is critical for the development of control strategies.
Collapse
Affiliation(s)
- Yusheng Guo
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Sergei Raev
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Maryssa K. Kick
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Molly Raque
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Linda J. Saif
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Anastasia N. Vlasova
- Center for Food Animal Health, Ohio Agricultural Research and Development Center, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
- Correspondence:
| |
Collapse
|
|
20
|
Hu L, Salmen W, Sankaran B, Lasanajak Y, Smith DF, Crawford SE, Estes MK, Prasad BVV. Novel fold of rotavirus glycan-binding domain predicted by AlphaFold2 and determined by X-ray crystallography. Commun Biol 2022; 5:419. [PMID: 35513489 PMCID: PMC9072675 DOI: 10.1038/s42003-022-03357-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 04/12/2022] [Indexed: 02/08/2023] Open
Abstract
The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping an α-helix represents a new fold for glycan recognition based on glycan array screening, which shows that VP8*B recognizes glycans containing N-acetyllactosamine moiety. Although uncommon, our study illustrates how evolution can incorporate structurally distinct folds with similar functionality in a homologous protein within the same virus genus.
Collapse
Affiliation(s)
- Liya Hu
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
| | - Wilhelm Salmen
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA
| | - Banumathi Sankaran
- Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, CA, USA
| | - Yi Lasanajak
- Emory Glycomics and Molecular Interactions Core (EGMIC), Emory University School of Medicine, Atlanta, GA, USA
| | - David F Smith
- Emory Glycomics and Molecular Interactions Core (EGMIC), Emory University School of Medicine, Atlanta, GA, USA
| | - Sue E Crawford
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Mary K Estes
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - B V Venkataram Prasad
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
| |
Collapse
|
|
21
|
Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation: A Pilot Study. Nutrients 2022; 14:nu14051014. [PMID: 35267989 PMCID: PMC8912797 DOI: 10.3390/nu14051014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/21/2022] [Accepted: 02/24/2022] [Indexed: 12/19/2022] Open
Abstract
Background: Human milk oligosaccharides are complex, non-digestible carbohydrates that directly interact with intestinal epithelial cells to alter barrier function and host inflammation. Oligosaccharide composition varies widely between individual mothers, but it is unclear if this inter-individual variation has any impact on intestinal epithelial barrier function and gut inflammation. Methods: Human milk oligosaccharides were extracted from the mature human milk of four individual donors. Using an in vitro model of intestinal injury, the effects of the oligosaccharides on the intestinal epithelial barrier and select innate and adaptive immune functions were assessed. Results: Individual oligosaccharide compositions shared comparable effects on increasing transepithelial electrical resistance and reducing the macromolecular permeability of polarized (Caco-2Bbe1) monolayers but exerted distinct effects on the localization of the intercellular tight junction protein zona occludins-1 in response to injury induced by a human enteric bacterial pathogen Escherichia coli, serotype O157:H7. Immunoblots showed the differential effects of oligosaccharide compositions in reducing host chemokine interleukin 8 expression and inhibiting of p38 MAP kinase activation. Conclusions: These results provide evidence of both shared and distinct effects on the host intestinal epithelial function that are attributable to inter-individual differences in the composition of human milk oligosaccharides.
Collapse
|
|
22
|
Amimo JO, Raev SA, Chepngeno J, Mainga AO, Guo Y, Saif L, Vlasova AN. Rotavirus Interactions With Host Intestinal Epithelial Cells. Front Immunol 2021; 12:793841. [PMID: 35003114 PMCID: PMC8727603 DOI: 10.3389/fimmu.2021.793841] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/06/2021] [Indexed: 12/13/2022] Open
Abstract
Rotavirus (RV) is the foremost enteric pathogen associated with severe diarrheal illness in young children (<5years) and animals worldwide. RV primarily infects mature enterocytes in the intestinal epithelium causing villus atrophy, enhanced epithelial cell turnover and apoptosis. Intestinal epithelial cells (IECs) being the first physical barrier against RV infection employs a range of innate immune strategies to counteract RVs invasion, including mucus production, toll-like receptor signaling and cytokine/chemokine production. Conversely, RVs have evolved numerous mechanisms to escape/subvert host immunity, seizing translation machinery of the host for effective replication and transmission. RV cell entry process involve penetration through the outer mucus layer, interaction with cell surface molecules and intestinal microbiota before reaching the IECs. For successful cell attachment and entry, RVs use sialic acid, histo-blood group antigens, heat shock cognate protein 70 and cell-surface integrins as attachment factors and/or (co)-receptors. In this review, a comprehensive summary of the existing knowledge of mechanisms underlying RV-IECs interactions, including the role of gut microbiota, during RV infection is presented. Understanding these mechanisms is imperative for developing efficacious strategies to control RV infections, including development of antiviral therapies and vaccines that target specific immune system antagonists within IECs.
Collapse
Affiliation(s)
- Joshua Oluoch Amimo
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
- Department of Animal Production, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya
| | - Sergei Alekseevich Raev
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Juliet Chepngeno
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Alfred Omwando Mainga
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
- Department of Public Health, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Nairobi, Nairobi, Kenya
| | - Yusheng Guo
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Linda Saif
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| | - Anastasia N. Vlasova
- Center for Food Animal Health, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, United States
| |
Collapse
|
|
23
|
Wu RY, Li B, Horne RG, Ahmed A, Lee D, Robinson SC, Zhu H, Cadete M, Alganabi M, Filler R, Johnson-Henry KC, Delgado-Olguin P, Pierro A, Sherman PM. Structure-Function Relationships of Human Milk Oligosaccharides on the Intestinal Epithelial Transcriptome in Caco-2 Cells and a Murine Model of Necrotizing Enterocolitis. Mol Nutr Food Res 2021; 66:e2100893. [PMID: 34921749 DOI: 10.1002/mnfr.202100893] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/06/2021] [Indexed: 12/24/2022]
Abstract
SCOPE Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency affecting preterm infants. Breastmilk protects against NEC, partly due to human milk oligosaccharides (HMOs). HMO compositions are highly diverse, and it is unclear if anti-NEC properties are specific to carbohydrate motifs. Here, this study compares intestinal epithelial transcriptomes of five synthetic HMOs (sHMOs) and examines structure-function relationships of HMOs on intestinal signaling. METHODS AND RESULTS This study interrogates the transcriptome of Caco-2Bbe1 cells in response to five synthetic HMOs (sHMOs) using RNA sequencing: 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3FL), 6'-siallyllactose (6'-SL), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT). Protection against intestinal barrier dysfunction and inflammation occurred in an HMO-dependent manner. Each sHMO exerts a unique set of host transcriptome changes and modulated unique signaling pathways. There is clustering between HMOs bearing similar side chains, with little overlap in gene regulation which is shared by all sHMOs. Interestingly, most sHMOs protect pups against NEC, exerting divergent mechanisms on intestinal cell morphology and inflammation. CONCLUSIONS These results demonstrate that while structurally distinct HMOs impact intestinal physiology, their mechanisms of action differ. This finding establishes the first structure-function relationship of HMOs in the context of intestinal cell signaling responses and offers a functional framework by which to screen and design HMO-like compounds.
Collapse
Affiliation(s)
- Richard Y Wu
- Cell Biology Program, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | - Bo Li
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada
| | - Rachael G Horne
- Cell Biology Program, The Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | - Abdalla Ahmed
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8, Canada
| | - Dorothy Lee
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | - Shaiya C Robinson
- Cell Biology Program, The Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | - Haitao Zhu
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.,Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Marissa Cadete
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | - Mashriq Alganabi
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | - Rachel Filler
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada
| | | | - Paul Delgado-Olguin
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8, Canada.,Heart & Stroke Richard Lewar Center of Excellence, Toronto, M5S 3H2, Canada
| | - Agostino Pierro
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.,Department of Molecular Genetics, University of Toronto, Toronto, M5S 1A8, Canada
| | - Philip M Sherman
- Cell Biology Program, The Hospital for Sick Children, Toronto, M5G 0A4, Canada.,Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, M5G 1X8, Canada
| |
Collapse
|
|
24
|
Peña-Gil N, Santiso-Bellón C, Gozalbo-Rovira R, Buesa J, Monedero V, Rodríguez-Díaz J. The Role of Host Glycobiology and Gut Microbiota in Rotavirus and Norovirus Infection, an Update. Int J Mol Sci 2021; 22:13473. [PMID: 34948268 PMCID: PMC8704558 DOI: 10.3390/ijms222413473] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/13/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open
Abstract
Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Several studies have demonstrated that histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. Polymorphisms in genes that code for enzymes required for HBGAs synthesis lead to secretor or non-secretor and Lewis positive or Lewis negative individuals. While secretor individuals appear to be more susceptible to RV infections, regarding NoVs infections, there are too many discrepancies that prevent the ability to draw conclusions. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection. Human trials with live, attenuated RV vaccines and analysis of the microbiota in responder and non-responder individuals also allowed the identification of bacterial taxa linked to vaccine efficacy. As more information is gained on the complex relationships that are established between the host (glycobiology and immune system), the gut microbiota and intestinal viruses, new avenues will open for the development of novel anti-NoV and anti-RV therapies.
Collapse
Affiliation(s)
- Nazaret Peña-Gil
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Cristina Santiso-Bellón
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Roberto Gozalbo-Rovira
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Javier Buesa
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| | - Vicente Monedero
- Department of Biotechnology, Institute of Agrochemistry and Food Technology (IATA-CSIC), 46980 Paterna, Spain;
| | - Jesús Rodríguez-Díaz
- Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez 17, 46010 Valencia, Spain; (N.P.-G.); (C.S.-B.); (R.G.-R.); (J.B.)
| |
Collapse
|
|
25
|
Swevers L, Kontogiannatos D, Kolliopoulou A, Ren F, Feng M, Sun J. Mechanisms of Cell Entry by dsRNA Viruses: Insights for Efficient Delivery of dsRNA and Tools for Improved RNAi-Based Pest Control. Front Physiol 2021; 12:749387. [PMID: 34858204 PMCID: PMC8632066 DOI: 10.3389/fphys.2021.749387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/11/2021] [Indexed: 12/18/2022] Open
Abstract
While RNAi is often heralded as a promising new strategy for insect pest control, a major obstacle that still remains is the efficient delivery of dsRNA molecules within the cells of the targeted insects. However, it seems overlooked that dsRNA viruses already have developed efficient strategies for transport of dsRNA molecules across tissue barriers and cellular membranes. Besides protecting their dsRNA genomes in a protective shell, dsRNA viruses also display outer capsid layers that incorporate sophisticated mechanisms to disrupt the plasma membrane layer and to translocate core particles (with linear dsRNA genome fragments) within the cytoplasm. Because of the perceived efficiency of the translocation mechanism, it is well worth analyzing in detail the molecular processes that are used to achieve this feat. In this review, the mechanism of cell entry by dsRNA viruses belonging to the Reoviridae family is discussed in detail. Because of the large amount of progress in mammalian versus insect models, the mechanism of infections of reoviruses in mammals (orthoreoviruses, rotaviruses, orbiviruses) will be treated as a point of reference against which infections of reoviruses in insects (orbiviruses in midges, plant viruses in hemipterans, insect-specific cypoviruses in lepidopterans) will be compared. The goal of this discussion is to uncover the basic principles by which dsRNA viruses cross tissue barriers and translocate their cargo to the cellular cytoplasm; such knowledge subsequently can be incorporated into the design of dsRNA virus-based viral-like particles for optimal delivery of RNAi triggers in targeted insect pests.
Collapse
Affiliation(s)
- Luc Swevers
- Insect Molecular Genetics and Biotechnology, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, Athens, Greece
| | - Dimitrios Kontogiannatos
- Insect Molecular Genetics and Biotechnology, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, Athens, Greece
| | - Anna Kolliopoulou
- Insect Molecular Genetics and Biotechnology, Institute of Biosciences and Applications, National Centre for Scientific Research “Demokritos”, Athens, Greece
| | - Feifei Ren
- Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Min Feng
- Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jingchen Sun
- Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China
| |
Collapse
|
|
26
|
Caddy S, Papa G, Borodavka A, Desselberger U. Rotavirus research: 2014-2020. Virus Res 2021; 304:198499. [PMID: 34224769 DOI: 10.1016/j.virusres.2021.198499] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/24/2021] [Accepted: 06/25/2021] [Indexed: 02/09/2023]
Abstract
Rotaviruses are major causes of acute gastroenteritis in infants and young children worldwide and also cause disease in the young of many other mammalian and of avian species. During the recent 5-6 years rotavirus research has benefitted in a major way from the establishment of plasmid only-based reverse genetics systems, the creation of human and other mammalian intestinal enteroids, and from the wide application of structural biology (cryo-electron microscopy, cryo-EM tomography) and complementary biophysical approaches. All of these have permitted to gain new insights into structure-function relationships of rotaviruses and their interactions with the host. This review follows different stages of the viral replication cycle and summarizes highlights of structure-function studies of rotavirus-encoded proteins (both structural and non-structural), molecular mechanisms of viral replication including involvement of cellular proteins and lipids, the spectrum of viral genomic and antigenic diversity, progress in understanding of innate and acquired immune responses, and further developments of prevention of rotavirus-associated disease.
Collapse
Affiliation(s)
- Sarah Caddy
- Cambridge Institute for Therapeutic Immunology and Infectious Disease Jeffery Cheah Biomedical Centre, Cambridge, CB2 0AW, UK.
| | - Guido Papa
- MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus Francis Crick Avenue, Cambridge, CB2 0QH, UK.
| | - Alexander Borodavka
- Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, UK.
| | - Ulrich Desselberger
- Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
| |
Collapse
|
|
27
|
Tenge VR, Hu L, Prasad BVV, Larson G, Atmar RL, Estes MK, Ramani S. Glycan Recognition in Human Norovirus Infections. Viruses 2021; 13:2066. [PMID: 34696500 PMCID: PMC8537403 DOI: 10.3390/v13102066] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 12/11/2022] Open
Abstract
Recognition of cell-surface glycans is an important step in the attachment of several viruses to susceptible host cells. The molecular basis of glycan interactions and their functional consequences are well studied for human norovirus (HuNoV), an important gastrointestinal pathogen. Histo-blood group antigens (HBGAs), a family of fucosylated carbohydrate structures that are present on the cell surface, are utilized by HuNoVs to initially bind to cells. In this review, we describe the discovery of HBGAs as genetic susceptibility factors for HuNoV infection and review biochemical and structural studies investigating HuNoV binding to different HBGA glycans. Recently, human intestinal enteroids (HIEs) were developed as a laboratory cultivation system for HuNoV. We review how the use of this novel culture system has confirmed that fucosylated HBGAs are necessary and sufficient for infection by several HuNoV strains, describe mechanisms of antibody-mediated neutralization of infection that involve blocking of HuNoV binding to HBGAs, and discuss the potential for using the HIE model to answer unresolved questions on viral interactions with HBGAs and other glycans.
Collapse
Affiliation(s)
- Victoria R. Tenge
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
| | - Liya Hu
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA;
| | - B. V. Venkataram Prasad
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
- Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Göran Larson
- Department of Laboratory Medicine, University of Gothenburg, SE 413 45 Gothenburg, Sweden;
| | - Robert L. Atmar
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Mary K. Estes
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Sasirekha Ramani
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; (V.R.T.); (B.V.V.P.); (R.L.A.); (M.K.E.)
| |
Collapse
|
|
28
|
Zweigart MR, Becker-Dreps S, Bucardo F, González F, Baric RS, Lindesmith LC. Serological Humoral Immunity Following Natural Infection of Children with High Burden Gastrointestinal Viruses. Viruses 2021; 13:2033. [PMID: 34696463 PMCID: PMC8538683 DOI: 10.3390/v13102033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/01/2021] [Accepted: 10/03/2021] [Indexed: 12/14/2022] Open
Abstract
Acute gastroenteritis (AGE) is a major cause of morbidity and mortality worldwide, resulting in an estimated 440,571 deaths of children under age 5 annually. Rotavirus, norovirus, and sapovirus are leading causes of childhood AGE. A successful rotavirus vaccine has reduced rotavirus hospitalizations by more than 50%. Using rotavirus as a guide, elucidating the determinants, breath, and duration of serological antibody immunity to AGE viruses, as well as host genetic factors that define susceptibility is essential for informing development of future vaccines and improving current vaccine candidates. Here, we summarize the current knowledge of disease burden and serological antibody immunity following natural infection to inform further vaccine development for these three high-burden viruses.
Collapse
Affiliation(s)
- Mark R. Zweigart
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA; (M.R.Z.); (S.B.-D.)
| | - Sylvia Becker-Dreps
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA; (M.R.Z.); (S.B.-D.)
- Department of Family Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Filemón Bucardo
- Department of Microbiology, National Autonomous University of Nicaragua, León 21000, Nicaragua; (F.B.); (F.G.)
| | - Fredman González
- Department of Microbiology, National Autonomous University of Nicaragua, León 21000, Nicaragua; (F.B.); (F.G.)
| | - Ralph S. Baric
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA; (M.R.Z.); (S.B.-D.)
| | - Lisa C. Lindesmith
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA; (M.R.Z.); (S.B.-D.)
| |
Collapse
|
|
29
|
Babji S, Sindhu KN, Selvarajan S, Ramani S, Venugopal S, Khakha SA, Hemavathy P, Ganesan SK, Giri S, Reju S, Gopalakrishnan K, Ninan B, Iturriza-Gomara M, Srikanth P, Kang G. Persistence of G10P[11] neonatal rotavirus infections in southern India. J Clin Virol 2021; 144:104989. [PMID: 34607240 PMCID: PMC8556361 DOI: 10.1016/j.jcv.2021.104989] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 09/06/2021] [Accepted: 09/23/2021] [Indexed: 12/16/2022]
Abstract
Background: Neonatal rotavirus infections are predominantly caused by distinct genotypes restricted to this age-group and are mostly asymptomatic. Method: Stool samples from neonates admitted for >48 h in neonatal intensive care units (NICUs) in Vellore (2014–2015) and Chennai (2015–2016) in southern India, and from neonates born at hospitals in Vellore but not admitted to NICUs (2015–2016) were tested for rotavirus by ELISA and genotyped by hemi-nested RT-PCR. Results: Of 791 neonates, 150 and 336 were recruited from Vellore and Chennai NICUs, and 305 were born in five hospitals in Vellore. Positivity rates in the three settings were 49.3% (74/150), 29.5% (99/336) and 54% (164/305), respectively. G10P[11] was the commonly identified genotype in 87.8% (65/74), 94.9% (94/99) and 98.2% (161/164) of the neonates in Vellore and Chennai NICUs, and those born at Vellore hospitals, respectively. Neonates delivered by lower segment cesarian section (LSCS) at Vellore hospitals, not admitted to NICUs, had a significantly higher odds of acquiring rotavirus infection compared to those delivered vaginally [p = 0.002, OR = 2.4 (1.4–4.3)]. Conclusions: This report demonstrates the persistence of G10P[11] strain in Vellore and Chennai, indicating widespread neonatal G10P[11] strain in southern India and their persistence over two decades, leading to interesting questions about strain stability.
Collapse
Affiliation(s)
- Sudhir Babji
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | | | - Sribal Selvarajan
- Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Sasirekha Ramani
- Baylor College of Medicine, Houston, TX, United States of America
| | - Srinivasan Venugopal
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Shainey Alokit Khakha
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Priya Hemavathy
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Santhosh Kumar Ganesan
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Sidhartha Giri
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Sudhabharathi Reju
- Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Krithika Gopalakrishnan
- Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Binu Ninan
- Department of Neonatology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Miren Iturriza-Gomara
- NIHR Health Protection Research Unit in Gastrointestinal Infections at University of Liverpool, Liverpool, United Kingdom of Great Britain
| | - Padma Srikanth
- Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Gagandeep Kang
- The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
| |
Collapse
|
|
30
|
Kanai Y, Kobayashi T. FAST Proteins: Development and Use of Reverse Genetics Systems for Reoviridae Viruses. Annu Rev Virol 2021; 8:515-536. [PMID: 34586868 DOI: 10.1146/annurev-virology-091919-070225] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Reverse genetics systems for viruses, the technology used to generate gene-engineered recombinant viruses from artificial genes, enable the study of the roles of the individual nucleotides and amino acids of viral genes and proteins in infectivity, replication, and pathogenicity. The successful development of a reverse genetics system for poliovirus in 1981 accelerated the establishment of protocols for other RNA viruses important for human health. Despite multiple efforts, rotavirus (RV), which causes severe gastroenteritis in infants, was refractory to reverse genetics analysis, and the first complete reverse genetics system for RV was established in 2017. This novel technique involves use of the fusogenic protein FAST (fusion-associated small transmembrane) derived from the bat-borne Nelson Bay orthoreovirus, which induces massive syncytium formation. Co-transfection of a FAST-expressing plasmid with complementary DNAs encoding RV genes enables rescue of recombinant RV. This review focuses on methodological insights into the reverse genetics system for RV and discusses applications and potential improvements to this system.
Collapse
Affiliation(s)
- Yuta Kanai
- Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; ,
| | - Takeshi Kobayashi
- Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; ,
| |
Collapse
|
|
31
|
Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens. Proc Natl Acad Sci U S A 2021; 118:2107963118. [PMID: 34475219 DOI: 10.1073/pnas.2107963118] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 08/02/2021] [Indexed: 12/27/2022] Open
Abstract
Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor-binding domains together with Lewis epitope-containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ββ and βα HBGA receptor-binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.
Collapse
|
|
32
|
Abstract
Histo-blood group antigen contains oligosaccharides that serve as receptors for norovirus (NoV) and rotavirus (RV). The receptors are only present on the surface of intestinal mucosal epithelial cells of secretors; therefore, secretors are susceptible to NoV and RV diarrhea and nonsecretors are resistant. The prevalence of secretors in different countries varies between 50% and 90%. Secretor rates evolved in response to environmental pressures such as infectious diseases.
Collapse
|
|
33
|
Lee SK, Oh SJ, Choi S, Choi SH, Shin SH, Lee EJ, Cho EJ, Hyun J, Kim HS. Relationship Between Rotavirus P[6] Infection in Korean Neonates and Histo-Blood Group Antigen: a Single-Center Study. Ann Lab Med 2021; 41:181-189. [PMID: 33063679 PMCID: PMC7591292 DOI: 10.3343/alm.2021.41.2.181] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 05/05/2020] [Accepted: 09/24/2020] [Indexed: 01/27/2023] Open
Abstract
Background Rotaviruses are a major cause of pediatric gastroenteritis. The rotavirus P[6] genotype is the most prevalent genotype isolated from Korean neonates but has rarely been reported in other countries. Histo-blood group antigen (HBGA) is known to play an important role in rotavirus infection. We investigated the relationship between rotavirus genotype and HBGA-Lewis blood type in Korean children and explored the reasons for the predominance of rotavirus P[6] strain in Korean neonates. Methods Blood and stool samples were collected from 16 rotavirus-infected patients. Rotavirus G (VP7) and P (VP4) genotyping was performed using reverse transcription-PCR and sequencing. Lewis antigen phenotypes (Lea/Leb) were tested, and HBGA-Lewis genotype was determined by sequencing the secretor (FUT2) and Lewis (FUT3) genes. Deduced amino acid sequences and three-dimensional structures of the VP8* portion of the rotavirus VP4 protein were analyzed. Results All P[6] rotaviruses were isolated from neonates under one month of age, who were negative or weakly positive for the Leb antigen. However, 10 of the 11 non-P[6] rotaviruses were isolated from older children who were Leb antigen-positive. The VP8* amino acid sequences differed among P[6], P[4], and P[8] genotypes. Korean P[6] strains showed a unique VP8* sequence with amino acid substitutions, including Y169 > L169, which differed from the sequences of P[6] strains from other countries. Conclusions The predominance of the rotavirus P[6] genotype in Korean neonates may be related to the interaction between HBGA-Lewis antigen and the VP8* portion of the VP4 protein, and this information will be helpful in future neonatal vaccine development.
Collapse
Affiliation(s)
- Su-Kyung Lee
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Su Jin Oh
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Seoheui Choi
- Department of Pediatrics, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Soo Han Choi
- Department of Pediatrics, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Seon-Hee Shin
- Department of Pediatrics, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Eun Jin Lee
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Eun-Jung Cho
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Jungwon Hyun
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Hyun Soo Kim
- Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| |
Collapse
|
|
34
|
Hoxie I, Dennehy JJ. Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns. Viruses 2021; 13:v13081460. [PMID: 34452326 PMCID: PMC8402926 DOI: 10.3390/v13081460] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 12/29/2022] Open
Abstract
Reassortment of the Rotavirus A (RVA) 11-segment dsRNA genome may generate new genome constellations that allow RVA to expand its host range or evade immune responses. Reassortment may also produce phylogenetic incongruities and weakly linked evolutionary histories across the 11 segments, obscuring reassortment-specific epistasis and changes in substitution rates. To determine the co-segregation patterns of RVA segments, we generated time-scaled phylogenetic trees for each of the 11 segments of 789 complete RVA genomes isolated from mammalian hosts and compared the segments’ geodesic distances. We found that segments 4 (VP4) and 9 (VP7) occupied significantly different tree spaces from each other and from the rest of the genome. By contrast, segments 10 and 11 (NSP4 and NSP5/6) occupied nearly indistinguishable tree spaces, suggesting strong co-segregation. Host-species barriers appeared to vary by segment, with segment 9 (VP7) presenting the weakest association with host species. Bayesian Skyride plots were generated for each segment to compare relative genetic diversity among segments over time. All segments showed a dramatic decrease in diversity around 2007 coinciding with the introduction of RVA vaccines. To assess selection pressures, codon adaptation indices and relative codon deoptimization indices were calculated with respect to different host genomes. Codon usage varied by segment with segment 11 (NSP5) exhibiting significantly higher adaptation to host genomes. Furthermore, RVA codon usage patterns appeared optimized for expression in humans and birds relative to the other hosts examined, suggesting that translational efficiency is not a barrier in RVA zoonosis.
Collapse
Affiliation(s)
- Irene Hoxie
- Biology Department, The Graduate Center, The City University of New York, New York, NY 10016, USA;
- Biology Department, Queens College, The City University of New York, Flushing, New York, NY 11367, USA
- Correspondence:
| | - John J. Dennehy
- Biology Department, The Graduate Center, The City University of New York, New York, NY 10016, USA;
- Biology Department, Queens College, The City University of New York, Flushing, New York, NY 11367, USA
| |
Collapse
|
|
35
|
Sun X, Li D, Duan Z. Structural Basis of Glycan Recognition of Rotavirus. Front Mol Biosci 2021; 8:658029. [PMID: 34307449 PMCID: PMC8296142 DOI: 10.3389/fmolb.2021.658029] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/21/2021] [Indexed: 11/13/2022] Open
Abstract
Rotavirus (RV) is an important pathogen causing acute gastroenteritis in young humans and animals. Attachment to the host receptor is a crucial step for the virus infection. The recent advances in illustrating the interactions between RV and glycans promoted our understanding of the host range and epidemiology of RVs. VP8*, the distal region of the RV outer capsid spike protein VP4, played a critical role in the glycan recognition. Group A RVs were classified into different P genotypes based on the VP4 sequences and recognized glycans in a P genotype-dependent manner. Glycans including sialic acid, gangliosides, histo-blood group antigens (HBGAs), and mucin cores have been reported to interact with RV VP8*s. The glycan binding specificities of VP8*s of different RV genotypes have been studied. Here, we mainly discussed the structural basis for the interactions between RV VP8*s and glycans, which provided molecular insights into the receptor recognition and host tropism, offering new clues to the design of RV vaccine and anti-viral agents.
Collapse
Affiliation(s)
- Xiaoman Sun
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, China.,National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
| | - Dandi Li
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, China.,National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
| | - Zhaojun Duan
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, China.,National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China
| |
Collapse
|
|
36
|
Arias CF, López S. Rotavirus cell entry: not so simple after all. Curr Opin Virol 2021; 48:42-48. [PMID: 33887683 DOI: 10.1016/j.coviro.2021.03.011] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 03/28/2021] [Accepted: 03/29/2021] [Indexed: 01/25/2023]
Abstract
Rotaviruses are important agents of severe gastroenteritis in young children, and show a very selective cell and tissue tropism, as well as significant age and host restriction. In the last few years, these properties have been associated with the initial interaction of the virus with histo-blood group antigens on the cell surface, although post-attachment interactions have also been found to define the susceptibility to infection of human enteroids. These initial interactions seem also to determine the virus entry pathway, as well as the induction of signaling cascades that influence the virus intracellular vesicular traffic and escape from endosomes. Here we review the current knowledge of the different stages of the virus entry journey.
Collapse
Affiliation(s)
- Carlos F Arias
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Colonia Chamilpa, Cuernavaca, Morelos, Mexico.
| | - Susana López
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Colonia Chamilpa, Cuernavaca, Morelos, Mexico
| |
Collapse
|
|
37
|
Muhialdin BJ, Zawawi N, Abdull Razis AF, Bakar J, Zarei M. Antiviral activity of fermented foods and their probiotics bacteria towards respiratory and alimentary tracts viruses. Food Control 2021; 127:108140. [PMID: 33867696 PMCID: PMC8036130 DOI: 10.1016/j.foodcont.2021.108140] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 03/09/2021] [Accepted: 04/04/2021] [Indexed: 02/06/2023]
Abstract
The recent COVID-19, a viral outbreak calls for a high demand for non-conventional antiviral agents that can reduce the risk of infections and promote fast recovery. Fermented foods and their probiotics bacteria have recently received increasing interest due to the reported potential of high antiviral activity. Several probiotics strains demonstrated broad range of antiviral activities and different mechanisms of action. This article will review the diversity, health benefits, interaction with immune system and antiviral activity of fermented foods and their probiotics bacteria. In addition, the mechanisms of action will be reviewed to determine the broad range potential antiviral activity against the respiratory and alimentary tracts viruses. The probiotics bacteria and bioactive compounds in fermented foods demonstrated antiviral activities against respiratory and alimentary tracts viruses. The mechanism of action was reported to be due to the stimulation of the immune system function via enhancing natural killers cell toxicity, enhance the production of pro-inflammatory cytokines, and increasing the cytotoxic of T lymphocytes (CD3+, CD16+, CD56+). However, further studies are highly recommended to determine the potential antiviral activity for traditional fermented foods.
Collapse
Affiliation(s)
- Belal J Muhialdin
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia.,Halal Products Research Institute, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia
| | - Norhasnida Zawawi
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia.,Natural Medicines and Product Research Laboratory, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia
| | - Ahmad Faizal Abdull Razis
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia.,Natural Medicines and Product Research Laboratory, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia
| | - Jamilah Bakar
- Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, UPM, Selangor, Malaysia
| | - Mohammad Zarei
- Department of Food Science and Technology, School of Industrial Technology, Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, 40450, Selangor, Malaysia
| |
Collapse
|
|
38
|
The effects of diet and gut microbiota on the regulation of intestinal mucin glycosylation. Carbohydr Polym 2021; 258:117651. [DOI: 10.1016/j.carbpol.2021.117651] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/06/2021] [Accepted: 01/11/2021] [Indexed: 12/13/2022]
|
|
39
|
Falkenhagen A, Huyzers M, van Dijk AA, Johne R. Rescue of Infectious Rotavirus Reassortants by a Reverse Genetics System Is Restricted by the Receptor-Binding Region of VP4. Viruses 2021; 13:v13030363. [PMID: 33668972 PMCID: PMC7996497 DOI: 10.3390/v13030363] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/11/2021] [Accepted: 02/22/2021] [Indexed: 12/22/2022] Open
Abstract
The rotavirus species A (RVA) capsid contains the spike protein VP4, which interacts with VP6 and VP7 and is involved in cellular receptor binding. The capsid encloses the genome consisting of eleven dsRNA segments. Reassortment events can result in novel strains with changed properties. Using a plasmid-based reverse genetics system based on simian RVA strain SA11, we previously showed that the rescue of viable reassortants containing a heterologous VP4-encoding genome segment was strain-dependent. In order to unravel the reasons for the reassortment restrictions, we designed here a series of plasmids encoding chimeric VP4s. Exchange of the VP4 domains interacting with VP6 and VP7 was not sufficient for rescue of viable viruses. In contrast, the exchange of fragments encoding the receptor-binding region of VP4 resulted in virus rescue. All parent strains and the rescued reassortants replicated efficiently in MA-104 cells used for virus propagation. In contrast, replication in BSR T7/5 cells used for plasmid transfection was only efficient for the SA11 strain, whereas the rescued reassortants replicated slowly, and the parent strains failing to produce reassortants did not replicate. While future research in this area is necessary, replication in BSR T7/5 cells may be one factor that affects the rescue of RVAs.
Collapse
Affiliation(s)
- Alexander Falkenhagen
- Department of Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany;
- Correspondence:
| | - Marno Huyzers
- Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, 2531 Potchefstroom, South Africa; (M.H.); (A.A.v.D.)
| | - Alberdina A. van Dijk
- Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, 2531 Potchefstroom, South Africa; (M.H.); (A.A.v.D.)
| | - Reimar Johne
- Department of Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany;
| |
Collapse
|
|
40
|
Zhao D, Liu Y, Huang P, Xia M, Li W, Tan M, Zhang X, Jiang X. Histo-blood group antigens as divergent factors of groups A and C rotaviruses circulating in humans and different animal species. Emerg Microbes Infect 2021; 9:1609-1617. [PMID: 32543972 PMCID: PMC7473324 DOI: 10.1080/22221751.2020.1782270] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Histo-blood group antigens (HBGAs) have been found to be important host susceptibility factors or receptors for human rotavirus (RVs) with genotype-specific host ranges, impacting the disease patterns, epidemiology, and strategy development against RV diseases in humans. However, how the glycan factors contribute to RV diversity and host ranges to different animal species remains unclear. In this study using recombinant VP8* proteins as probes to perform glycan array analyses of RVs, we observed a wide range of glycan-binding profiles, including those binding to sialic acid-containing glycans, among group A (RVA) and group C (RVC) RVs that mainly infect different animal species. A tri-saccharide glycan Galα1-3Galβ1-4Glc containing a terminal α-Gal was recognised by multiple RVA/RVC genotypes, providing valuable information on RV evolution under selection of the step-wisely synthesised HBGAs in many animals before they were introduced to humans to be human pathogens. Saliva binding studies of VP8* also revealed strain-specific host ranges or species barriers between humans and these animal RV genotypes, further improved our understanding on RV host ranges, disease burdens, epidemiology, and vaccine strategy against RVs.
Collapse
Affiliation(s)
- Dandan Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangdong, People's Republic of China
| | - Yang Liu
- Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ming Xia
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Weiwei Li
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - XuFu Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangdong, People's Republic of China
| | - Xi Jiang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Department of pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| |
Collapse
|
|
41
|
Infection of porcine small intestinal enteroids with human and pig rotavirus A strains reveals contrasting roles for histo-blood group antigens and terminal sialic acids. PLoS Pathog 2021; 17:e1009237. [PMID: 33513201 PMCID: PMC7846020 DOI: 10.1371/journal.ppat.1009237] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 12/15/2020] [Indexed: 01/19/2023] Open
Abstract
Rotaviruses (RVs) are a leading cause of acute viral gastroenteritis in young children and livestock worldwide. Growing evidence suggests that host cellular glycans, such as histo-blood group antigens (HBGAs) and sialic acids (SA), are recognized by the RV surface protein VP4. However, a mechanistic understanding of these interactions and their effects on RV infection and pathogenesis is lacking. Here, we established a porcine crypt-derived 3Dintestinalenteroids (PIEs) culture system which contains all intestinal epithelial cells identified in vivo and represents a unique physiologically functional model to study RV-glycan interactions in vitro. PIEs expressing different HBGAs (A+, H+, and A+/H+) were established and isolation, propagation, differentiation and RV infection conditions were optimized. Differentiated PIEs were infected with human RV (HRV) G1P[8] Wa, porcine RV (PRV) G9P[13], PRV Gottfried G4P[6] or PRV OSU G5P[7] virulent and attenuated strains and virus replication was measured by qRT-PCR. Our results indicated that virulent HRV G1P[8] Wa replicated to the highest titers in A+ PIEs, while a distinct trend was observed for PRV G9P[13] or G5P[7] with highest titers in H+ PIEs. Attenuated Wa and Gottfried strains replicated poorly in PIEs while the replication of attenuated G9P[13] and OSU strains in PIEs was relatively efficient. However, the replication of all 4 attenuate strains was less affected by the PIE HBGA phenotypes. HBGA synthesis inhibitor 2-F-Peracetyl-Fucose (2F) treatment demonstrated that HBGAs are essential for G1P[8] Wa replication; however, they may only serve as a cofactor for PRVs G9P[13] and OSU G5P[7]. Interestingly, contrasting outcomes were observed following sialidase treatment which significantly enhanced G9P[13] replication, but inhibited the growth of G5P[7]. These observations suggest that some additional receptors recognized by G9P[13] become unmasked after removal of terminal SA. Overall, our results confirm that differential HBGAs-RV and SA-RV interactions determine replication efficacy of virulent group A RVs in PIEs. Consequently, targeting individual glycans for development of therapeutics may not yield uniform results for various RV strains. Cell surface glycans, including histo-blood group antigens (HBGA) and sialic acids (SAs), have been shown to serve as receptors/attachment factors for many pathogens including RVs. However, how those glycans affect RV replication remains largely unknown due the lack of reliable in vitro models. To solve this problem, we established a 3D porcine intestinal enteroid (PIE) model that recapitulates the complex intestinal morphology better than conventional cell lines. By utilizing PIEs expressing different types of HBGAs, we found that several RV strains including Wa G1P[8], OSU G5P[7] and G9P[13] show preference for certain HBGA types. Interestingly, only Wa replication was reduced when HBGAs synthesis was inhibited, while that of OSU and G9P[13] was only marginally affected, which indicates that they may utilize alternative attachment factors for infection. Sialidase treatment strongly inhibited the growth of OSU, while G9P[13] replication was significantly enhanced. These findings suggest that SAs play contrasting roles in the infection of PRV OSU and G9P[13] strains. Overall, our studies demonstrate that PIEs can serve as a model to study pathogen-glycan interactions and suggest that genetically distinct RVs have evolved diverse mechanisms of cell attachment and/or entry.
Collapse
|
|
42
|
Human group A rotavirus P[25] VP8* specifically binds to A-type histo-blood group antigen. Virology 2021; 555:56-63. [PMID: 33453651 DOI: 10.1016/j.virol.2020.12.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 11/12/2020] [Accepted: 12/24/2020] [Indexed: 11/21/2022]
Abstract
Rotavirus (RV) is a common cause of acute gastroenteritis in young children. While P[8] and P[4] are the most prevalent RV genotypes in humans, other genotypes are also reported in human infections occasionally, including human P[25]. The glycan binding and structural characteristics of human P[25] were explored in our study. Human P[25] VP8* recognized type A histo-blood group antigen (HBGA) in the glycan microarray/oligosaccharide binding assay and could specifically hemagglutinate type A blood cells. Moreover, the P[25] VP8* structure was determined at 2.6 Å, revealing a similar conformation and a conserved putative glycan binding site as that of P[14] VP8*. This study provided further knowledge of the glycan binding and structural features of P[25] RV VP8*, promoting our understanding of the infection, prevalence, and host range of the P[III] RVs.
Collapse
|
|
43
|
Wang JX, Chen LN, Zhang CJ, Zhou HL, Zhang YH, Zhang XJ, Hao ZY, Qiu C, Ma JC, Zhao YL, Zhong W, Tan M, Jiang X, Wang SM, Wang XY. Genetic susceptibility to rotavirus infection in Chinese children: a population-based case-control study. Hum Vaccin Immunother 2020; 17:1803-1810. [PMID: 33295824 DOI: 10.1080/21645515.2020.1835121] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Rotaviruses (RVs) are the leading cause of acute gastroenteritis in children, while histo-blood group antigens (HBGAs) are believed to be host attachment and susceptibility factors of RVs. A large case-control study nested in a population-based diarrhea surveillance targeting children <5 y of age was performed in rural Hebei province, north China. Saliva and serum samples were collected from all participants to determine HBGA phenotyping, FUT2 mutations, and RV IgG antibody titers. A logistic model was employed to assess the association between host HBGA secretor status and risk of RV infection. Among 235 RV cases and 680 non-diarrhea controls studied, 82.4% of participants were IgG positive by an average age of 77 months. Out of the 235 RV cases, 216 (91.9%) were secretors, whereas the secretor rate was 76.3% in the non-diarrhea controls, resulted in an adjusted OR of 3.0 (95%CI: 1.9-4.7, P < .0001) between the two groups. Our population-based case-control study indicated a strong association between host HBGA secretor status and risk of RV infection in Chinese children. The high prevalence of Lewis-positive secretor status strongly suggests that Chinese children may be genetically susceptible to current co-circulating RV strains, and thus, a universal childhood immunization program against RV disease should be successful in China.
Collapse
Affiliation(s)
- Jin-Xia Wang
- Key Laboratory Medical Molecular Virology, MoE/MoH, and the Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Li-Na Chen
- Key Laboratory Medical Molecular Virology, MoE/MoH, and the Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Can-Jing Zhang
- Key Laboratory Medical Molecular Virology, MoE/MoH, and the Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Hong-Lu Zhou
- Key Laboratory Medical Molecular Virology, MoE/MoH, and the Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Yan-Hong Zhang
- Department of Hepatitis, Zhengding County Center for Disease Control and Prevention, Zhengding, People's Republic of China
| | - Xin-Jiang Zhang
- Department of Hepatitis, Zhengding County Center for Disease Control and Prevention, Zhengding, People's Republic of China
| | - Zhi-Yong Hao
- Department of Hepatitis, Zhengding County Center for Disease Control and Prevention, Zhengding, People's Republic of China
| | - Chao Qiu
- Key Laboratory Medical Molecular Virology, MoE/MoH, and the Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Jing-Chen Ma
- Vaccine Clinical Research Institute,Hebei Province Center for Disease Control and Prevention, Shijiazhuang, People's Republic of China
| | - Yu-Liang Zhao
- Vaccine Clinical Research Institute,Hebei Province Center for Disease Control and Prevention, Shijiazhuang, People's Republic of China
| | - Weiming Zhong
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,University of Cincinnati, College of Medicine, Cincinnati, OH, OH, USA
| | - Xi Jiang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,University of Cincinnati, College of Medicine, Cincinnati, OH, OH, USA
| | - Song-Mei Wang
- Laboratory of Molecular Biology, Training Center of Medical Experiments, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Xuan-Yi Wang
- Key Laboratory Medical Molecular Virology, MoE/MoH, and the Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.,Children's Hospital, Fudan University, Shanghai, People's Republic of China
| |
Collapse
|
|
44
|
|
|
45
|
FUT2 Secretor Status Influences Susceptibility to VP4 Strain-Specific Rotavirus Infections in South African Children. Pathogens 2020; 9:pathogens9100795. [PMID: 32992488 PMCID: PMC7601103 DOI: 10.3390/pathogens9100795] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/16/2020] [Accepted: 09/22/2020] [Indexed: 11/17/2022] Open
Abstract
Gastroenteritis is a preventable cause of morbidity and mortality worldwide. Rotavirus vaccination has significantly reduced the disease burden, but the sub-optimal vaccine efficacy observed in low-income regions needs improvement. Rotavirus VP4 'spike' proteins interact with FUT2-defined, human histo-blood group antigens on mucosal surfaces, potentially influencing strain circulation and the efficacy of P[8]-based rotavirus vaccines. Secretor status was investigated in 500 children <5 years-old hospitalised with diarrhoea, including 250 previously genotyped rotavirus-positive cases (P[8] = 124, P[4] = 86, and P[6] = 40), and 250 rotavirus-negative controls. Secretor status genotyping detected the globally prevalent G428A single nucleotide polymorphism (SNP) and was confirmed by Sanger sequencing in 10% of participants. The proportions of secretors in rotavirus-positive cases (74%) were significantly higher than in the rotavirus-negative controls (58%; p < 0.001). The rotavirus genotypes P[8] and P[4] were observed at significantly higher proportions in secretors (78%) than in non-secretors (22%), contrasting with P[6] genotypes with similar proportions amongst secretors (53%) and non-secretors (47%; p = 0.001). This suggests that rotavirus interacts with secretors and non-secretors in a VP4 strain-specific manner; thus, secretor status may partially influence rotavirus VP4 wild-type circulation and P[8] rotavirus vaccine efficacy. The study detected a mutation (rs1800025) ~50 bp downstream of the G428A SNP that would overestimate non-secretors in African populations when using the TaqMan® SNP Genotyping Assay.
Collapse
|
|
46
|
Sero-epidemiological study of the rotavirus VP8* protein from different P genotypes in Valencia, Spain. Sci Rep 2020; 10:7753. [PMID: 32385405 PMCID: PMC7210269 DOI: 10.1038/s41598-020-64767-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 04/22/2020] [Indexed: 11/12/2022] Open
Abstract
The aims of the present work were to determine the prevalence and titer of serum antibodies against several rotavirus VP8* proteins from different P genotypes in children and adults in Valencia, Spain; and to determine the role of the secretor status (FUT2G428A polymorphism) in the antibody response. The VP8* protein from the P[4], P[6], P[8], P[9], P[11], P[14] and P[25] genotypes were produced in E. coli. These proteins were tested with 88 serum samples from children (n = 41, 3.5 years old in average) and from adults (n = 47, 58 years old in average) by ELISA. A subset of 55 samples were genotyped for the FUT2G428A polymorphism and the antibody titers compared. The same subset of samples was also analysed by ELISA using whole rotavirus Wa particles (G1P[8]) as antigen. Ninety-three per cent of the samples were positive for at least one of the VP8* antigens. Differences in the IgG seroprevalence were found between children and adults for the P[4], P[8] and P[11] genotypes. Similarly, significant differences were found between adults and children in their antibody titers against the P[4], P[8], and P[11] VP8* genotypes, having the children higher antibody titers than adults. Interestingly, positive samples against rare genotypes such as P[11] (only in children), P[14] and P[25] were found. While no statistical differences in the antibody titers between secretors and non-secretors were found for any of the tested P genotypes studied, a higher statistic significant prevalence for the P[25] genotype was found in secretors compared to non-secretors. Significant differences in the antibody titers between secretors and non-secretors were found when the whole viral particles from the Wa rotavirus strain (G1P[8]) were used as the antigen.
Collapse
|
|
47
|
Sun X, Dang L, Li D, Qi J, Wang M, Chai W, Zhang Q, Wang H, Bai R, Tan M, Duan Z. Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus. Virol Sin 2020; 35:156-170. [PMID: 31620994 PMCID: PMC7198667 DOI: 10.1007/s12250-019-00164-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 08/21/2019] [Indexed: 10/25/2022] Open
Abstract
Rotavirus (RV) causes acute gastroenteritis in infants and children worldwide. Recent studies showed that glycans such as histo-blood group antigens (HBGAs) function as cell attachment factors affecting RV host susceptibility and prevalence. P[8] is the predominant RV genotype in humans, but the structural basis of how P[8] RVs interact with glycan ligands remains elusive. In this study, we characterized the interactions between P[8] VP8*s and glycans which showed that VP8*, the RV glycan binding domain, recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays. Importantly, we determined the structural basis of P[8] RV-glycans interaction from the crystal structures of a Rotateq P[8] VP8* in complex with core 2 and H type 1 glycans at 1.8 Å and 2.3 Å, respectively, revealing a common binding pocket and similar binding mode. Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[II] genogroup, while genotype-specific amino acid variations determined different glycan binding preference. Our data elucidated the detailed structural basis of the interactions between human P[8] RVs and different host glycan factors, shedding light on RV infection, epidemiology, and development of anti-viral agents.
Collapse
Affiliation(s)
- Xiaoman Sun
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Lei Dang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
- Inner Mongolia Medical University, Huhehaote, 010059, China
| | - Dandi Li
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Jianxun Qi
- Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Mengxuan Wang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Wengang Chai
- Glycosciences Laboratory, Department of Medicine, Imperial College London, London, UK
| | - Qing Zhang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Hong Wang
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China
| | - Ruixia Bai
- Inner Mongolia Medical University, Huhehaote, 010059, China
| | - Ming Tan
- Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Zhaojun Duan
- National Health Commission Key Laboratory for Medical Virology and Viral Diseases, Beijing, 102206, China.
- National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China.
| |
Collapse
|
|
48
|
Xu S, Ahmed LU, Stuckert MR, McGinnis KR, Liu Y, Tan M, Huang P, Zhong W, Zhao D, Jiang X, Kennedy MA. Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens. PLoS Pathog 2020; 16:e1008386. [PMID: 32208455 PMCID: PMC7122821 DOI: 10.1371/journal.ppat.1008386] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 04/03/2020] [Accepted: 02/05/2020] [Indexed: 11/19/2022] Open
Abstract
Initial cell attachment of rotavirus (RV) to specific cell surface glycan receptors, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b (Leb) and H type 1 antigens, however, the molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) spectroscopy-based titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb (LNDFH I) and type 1 HBGAs. We also used X-ray crystallography to determine the molecular details underlying P[6] recognition of H type 1 HBGAs. Unlike P[6]/P[19] VP8*s that recognize H type 1 HBGAs in a binding surface composed of an α-helix and a β-sheet, referred as the “βα binding site”, the P[8] and P[4] VP8*s bind Leb HBGAs in a previously undescribed pocket formed by the edges of two β-sheets, referred to as the “ββ binding site”. Importantly, the P[8] and P[4] VP8*s retain binding capability to non-Leb type 1 HBGAs using the βα binding site. The presence of two distinct binding sites for Leb and non-Leb HBGA glycans in the P[8] and P[4] VP8* domains suggests host-pathogen co-evolution under structural and functional adaptation of RV pathogens to host glycan polymorphisms. Assessment and understanding of the precise impact of this co-evolutionary process in determining RV host ranges and cross-species RV transmission should facilitate improved RV vaccine development and prediction of future RV strain emergence and epidemics. Rotaviruses (RV)s are the main cause of severe diarrhea in humans and animals. Significant advances in understanding RV diversity, evolution and epidemiology have been made after discovering that RVs recognize histo-blood group antigens (HBGAs) as host cell receptors or attachment factors. While different RV strains are known to have distinct binding preferences for HBGA receptor ligands, their molecular basis in controlling strain-specific host ranges remains unclear. In this study, we used solution nuclear magnetic resonance spectroscopy and X-ray crystallography to determine the molecular-level details for interactions of the human P[8] and P[6] RV VP8* domains with their HBGA receptors ligands. The distinct binding patterns observed between these major human RVs and their respective glycan ligands provide insight into the evolutionary relationships between different P[II] genotypes that ultimately determine host ranges, disease burden, zoonosis and epidemiology, which may impact future strategies for development of vaccines to protect against RV infections.
Collapse
Affiliation(s)
- Shenyuan Xu
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, United States of America
| | - Luay U. Ahmed
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, United States of America
| | - Michael Robert Stuckert
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, United States of America
| | - Kristen Rose McGinnis
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, United States of America
| | - Yang Liu
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
- Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Ming Tan
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
- University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
| | - Pengwei Huang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
| | - Weiming Zhong
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
| | - Dandan Zhao
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
| | - Xi Jiang
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America
- University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
- * E-mail: (XJ); (MAK)
| | - Michael A. Kennedy
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, United States of America
- * E-mail: (XJ); (MAK)
| |
Collapse
|
|
49
|
The Impact of Human Genetic Polymorphisms on Rotavirus Susceptibility, Epidemiology, and Vaccine Take. Viruses 2020; 12:v12030324. [PMID: 32192193 PMCID: PMC7150750 DOI: 10.3390/v12030324] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 03/13/2020] [Accepted: 03/14/2020] [Indexed: 12/16/2022] Open
Abstract
Innate resistance to viral infections can be attributed to mutations in genes involved in the immune response, or to the receptor/ligand. A remarkable example of the latter is the recently described Mendelian trait resistance to clinically important and globally predominating genotypes of rotavirus, the most common agent of severe dehydrating gastroenteritis in children worldwide. This resistance appears to be rotavirus genotype-dependent and is mainly mediated by histo-blood group antigens (HBGAs), which function as a receptor or attachment factors on gut epithelial surfaces. HBGA synthesis is mediated by fucosyltransferases and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis), and ABO (H) genes on chromosome 19. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. This genetic diversity has an effect on genotype-specific susceptibility, molecular epidemiology, and vaccine take. Here, we will discuss studies on genetic susceptibility to rotavirus infection and place them in the context of population susceptibility, rotavirus epidemiology, vaccine take, and public health impact.
Collapse
|
|
50
|
Boniface K, Byars SG, Cowley D, Kirkwood CD, Bines JE. Human Neonatal Rotavirus Vaccine (RV3-BB) Produces Vaccine Take Irrespective of Histo-Blood Group Antigen Status. J Infect Dis 2020; 221:1070-1078. [PMID: 31763671 PMCID: PMC7075413 DOI: 10.1093/infdis/jiz333] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 07/03/2019] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND VP4 [P] genotype binding specificities of rotaviruses and differential expression of histo-blood group antigens (HBGAs) between populations may contribute to reduced efficacy against severe rotavirus disease. P[6]-based rotavirus vaccines could broaden protection in such settings, particularly in Africa, where the Lewis-negative phenotype and P[6] rotavirus strains are common. METHODS The association between HBGA status and G3P[6] rotavirus vaccine (RV3-BB) take was investigated in a phase 2A study of RV3-BB vaccine involving 46 individuals in Dunedin, New Zealand, during 2012-2014. FUT2 and FUT3 genotypes were determined from DNA extracted from stool specimens, and frequencies of positive cumulative vaccine take, defined as an RV3-BB serum immune response (either immunoglobulin A or serum neutralizing antibody) and/or stool excretion of the vaccine strain, stratified by HBGA status were determined. RESULTS RV3-BB produced positive cumulative vaccine take in 29 of 32 individuals (91%) who expressed a functional FUT2 enzyme (the secretor group), 13 of 13 (100%) who were FUT2 null (the nonsecretor group), and 1 of 1 with reduced FUT2 activity (i.e., a weak secretor); in 37 of 40 individuals (93%) who expressed a functional FUT3 enzyme (the Lewis-positive group) and 3 of 3 who were FUT3 null (the Lewis-negative group); and in 25 of 28 Lewis-positive secretors (89%), 12 of 12 Lewis-positive nonsecretors (100%), 2 of 2 Lewis-negative secretors, and 1 of 1 Lewis-negative weak secretor. CONCLUSIONS RV3-BB produced positive cumulative vaccine take irrespective of HBGA status. RV3-BB has the potential to provide an improved level of protection in settings where P[6] rotavirus disease is endemic, irrespective of the HBGA profile of the population.
Collapse
Affiliation(s)
- Karen Boniface
- Enteric Diseases Group, Murdoch Children’s Research Institute, Seattle, Washington
| | - Sean G Byars
- Melbourne School of Population and Global Health, Seattle, Washington
| | - Daniel Cowley
- Enteric Diseases Group, Murdoch Children’s Research Institute, Seattle, Washington
- Department of Pediatrics, University of Melbourne, Seattle, Washington
| | - Carl D Kirkwood
- Enteric Diseases Group, Murdoch Children’s Research Institute, Seattle, Washington
- Department of Pediatrics, University of Melbourne, Seattle, Washington
- Bill and Melinda Gates Foundation, Seattle, Washington
| | - Julie E Bines
- Enteric Diseases Group, Murdoch Children’s Research Institute, Seattle, Washington
- Department of Pediatrics, University of Melbourne, Seattle, Washington
- Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital, Parkville, Australia
| |
Collapse
|