|
1
|
Ansil BR, Sanyal A, Sreenivas D, Garg KM, Ramakrishnan U, Chattopadhyay B. Identification of Distinct Rodent-Associated Adenovirus Lineages from Mixed-Use Landscape. ECOHEALTH 2025; 22:5-10. [PMID: 39903359 DOI: 10.1007/s10393-025-01700-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 12/15/2024] [Accepted: 12/25/2024] [Indexed: 02/06/2025]
Abstract
Land-use change and increased human-livestock-wildlife interactions have generated numerous possibilities for viral spillover, demanding enhanced surveillance in biodiverse regions. We investigated adenovirus diversity in small mammals, an understudied host taxon, from a forest-plantation mosaic in the Western Ghats biodiversity hotspot. We observed high prevalence (up to 39.39%) and identified five lineages of adenoviruses with unique mutations in the dominant small mammal species, Rattus satarae. These lineages significantly differed from other known murine adenoviruses (p-distance > 25%), indicating the likelihood of novel adenoviruses in this endemic small mammal and suggesting potential for unexplored DNA virus diversity in the region.
Collapse
Affiliation(s)
- B R Ansil
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India
| | - Avirup Sanyal
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India
- Trivedi School of Biosciences, Ashoka University, Sonipat, Haryana, 131029, India
| | - Darshan Sreenivas
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India
| | - Kritika M Garg
- Department of Biology, Ashoka University, Sonipat, Haryana, 131029, India
- Centre for Interdisciplinary Archaeological Research, Ashoka University, Sonipat, Haryana, 131029, India
| | - Uma Ramakrishnan
- National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India
| | - Balaji Chattopadhyay
- Trivedi School of Biosciences, Ashoka University, Sonipat, Haryana, 131029, India.
- Department of Biology, Ashoka University, Sonipat, Haryana, 131029, India.
| |
Collapse
|
|
2
|
Angel NZ, Sullivan MJ, Alsheikh-Hussain A, Fang L, MacDonald S, Pribyl A, Wills B, Tyson GW, Hugenholtz P, Parks DH, Griffin P, Wood DLA. Metagenomics: a new frontier for routine pathology testing of gastrointestinal pathogens. Gut Pathog 2025; 17:4. [PMID: 39827146 PMCID: PMC11742996 DOI: 10.1186/s13099-024-00673-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 12/24/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Accurate and comprehensive identification of enteropathogens, causing infectious gastroenteritis, is essential for optimal patient treatment and effective isolation processes in health care systems. Traditional diagnostic techniques are well established and optimised in low-cost formats. However, thorough testing for a wider range of causal agents is time consuming and remains limited to a subset of pathogenic organisms. Metagenomic next-generation sequencing (mNGS) allows the identification of all pathogens in a sample in a single test, without a reliance on culture or introduction of target selection bias. This study aims to determine the ability to routinely apply mNGS testing, in comparison to traditional culture or polymerase chain reaction (PCR) based tests, for the identification of causal pathogens for gastrointestinal infections. RESULTS The performance of mNGS, PCR and microscopy, culture and sensitivity (MCS) assays was established using 2,619 prospectively collected faecal samples from patients with symptomology indicative of infectious gastroenteritiss. Commonly experienced pathogens including Aeromonas spp, Campylobacter spp, Salmonella spp and Giardia spp, in single and co-infected patients, were used to establish test outcomes. When testing for these organisms, using the combined result from either or both PCR and MCS testing as the comparator, the mNGS assay had clinically acceptable sensitivity (89.2-100%). Further, the mNGS assay detected 14 additional enteropathogens, that were either not detected or not tested, by initial PCR/MCS testing. CONCLUSIONS The advantage of mNGS compared to other syndromic testing systems is the broad range of detectable targets and the ability to interrogate samples without clinician informed or assay specific bias. With the development of newer sequencing assays, it is now feasible to test for a wide range of target organisms in a sample using a single mNGS test. Overall, the mNGS based approach enabled pathogen detection that was comparable to conventional diagnostics and was shown to have the potential to be extended for the detection of many pathogens and genes of clinical interest. In conclusion, the mNGS assay offers an easy, sample to answer workflow with rapid detection of enteropathogens and has the potential to improve diagnosis, therapy and infection control precautions.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Gene W Tyson
- Microba Pty Ltd, Brisbane, Australia
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Philip Hugenholtz
- Microba Pty Ltd, Brisbane, Australia
- Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia
| | | | - Paul Griffin
- Microba Pty Ltd, Brisbane, Australia
- Department of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Mater Research Raymond Terrace, South Brisbane, Australia
| | | |
Collapse
|
|
3
|
Ito S, Takano C, Hoque SA, Shimizu-Onda Y, Okitsu S, Komoto S, Hayakawa S, Komine-Aizawa S, Khamrin P, Hanaoka N, Ushijima H. FilmArray® effectively detects all clades of F41 but encounters challenges with other adenovirus species. J Infect Chemother 2025; 31:102626. [PMID: 39818269 DOI: 10.1016/j.jiac.2025.102626] [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: 11/20/2024] [Revised: 01/06/2025] [Accepted: 01/10/2025] [Indexed: 01/18/2025]
Abstract
The BioFire FilmArray® Gastrointestinal (GI) Panel, a widely used diagnostic tool, is designed to detect the genetic material of 22 common pathogens responsible for gastroenteritis, including viruses, bacteria, and parasites. It can detect human adenovirus (HAdV) species F, particularly serotypes F40 and F41, which are the major causes of diarrhea and mortality in children. However, its potential shortcomings in detecting other HAdV species limit its effectiveness in broader HAdV detection in clinical settings and outbreak investigations. The aim of this study was to evaluate the ability of the GI Panel to detect three clades of HAdV-F41 and other HAdV species (viz., A31, B3, C1, C2, C5, C2/6, and D56) in Japan. Eighteen stool samples were analyzed, five of which contained HAdV-F41, and 13 contained other HAdV species, as confirmed via PCR and sequencing. Although the GI Panel reliably detected all clades of HAdV-F41, it failed to detect any other species, highlighting its limited diagnostic utility beyond F40/41 serotypes. Considering the high false-negative rate for non-F40/41 species, integrating complementary diagnostic methods such as PCR is crucial for comprehensive HAdV detection. These findings underscore the limitations of the GI Panel in detecting non-F40/41 species, such as HAdV-C (commonly associated with pediatric gastroenteritis) and other species that are important in immunocompromised patients. Complementary diagnostic methods, such as PCR or immunochromatographic assays, are essential to ensure accurate HAdV detection, especially in vulnerable populations.
Collapse
Affiliation(s)
- Shun Ito
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan; Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Chika Takano
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan; Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Sheikh Ariful Hoque
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan; Cell and Tissue Culture Laboratory, Center for Advanced Research in Sciences (CARS), University of Dhaka, Bangladesh
| | - Yuko Shimizu-Onda
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
| | - Shoko Okitsu
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
| | - Satoshi Komoto
- Division of One Health, Research Center for GLOBAL and LOCAL Infectious Diseases (RCGLID), Oita University, Yufu, Oita, Japan
| | | | - Shihoko Komine-Aizawa
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
| | - Pattara Khamrin
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan; Department of Microbiology, Faculty of Medicine, and Emerging and Re-emerging Diarrheal Viruses Research Center, Chiang Mai University, Chiang Mai, Thailand
| | - Nozomu Hanaoka
- Center for Emergency Preparedness and Response, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hiroshi Ushijima
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
| |
Collapse
|
|
4
|
Liu S, Hu Y, Xu W, Liu W, Wang B, Zeng X, Shao Z, Yang C, Xiong L, Cai X. Restoration of lysosomal function attenuates autophagic flux impairment in nucleus pulposus cells and protects against mechanical overloading-induced intervertebral disc degeneration. Autophagy 2024:1-17. [PMID: 39675125 DOI: 10.1080/15548627.2024.2440844] [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: 04/22/2024] [Revised: 12/04/2024] [Accepted: 12/06/2024] [Indexed: 12/17/2024] Open
Abstract
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain that incurs large socioeconomic burdens. Growing evidence reveals that macroautophagy/autophagy dysregulation contributes to IVDD, but the exact role of autophagy and its regulatory mechanisms remain largely unknown. Here, we found that mechanical overloading impaired the autophagic flux of nucleus pulposus (NP) cells in vivo and in vitro. Mechanistically, the impairment of autophagic flux was attributed to lysosomal dysfunction induced by overloading. Overloading could also lead to lysosomal membrane permeabilization and consequent lysosome-dependent cell death. As critical effectors of lysosomal quality control pathways, CHMP4B (charged multivesicular body protein 4B) and TFEB (transcription factor EB) were downregulated in overloading-treated NP cells and degenerative discs. Restoring lysosomal function by CHMP4B or TFEB overexpression attenuated autophagic flux impairment of NP cells and protected against overloading-induced IVDD. Additionally, human IVDD was associated with impaired autophagy, and defective lysosomal quality control was also linked to human IVDD. Collectively, these findings highlighted that lysosomal defects were crucial for mechanical overloading-induced autophagic flux impairment and death of NP cells, suggesting the potential therapeutic relevance of restoring lysosomal function for IVDD.Abbreviations: ADAMTS4: ADAM metallopeptidase with thrombospondin type 1 motif 4; Ad: adenovirus; AO: acridine orange; BafA1: bafilomycin A1; CHMP4B: charged multivesicular body protein 4B; CTSD: cathepsin D; CV%: coefficient of variation; DMSO: dimethyl sulfoxide; ESCRT: endosomal sorting complex required for transport; HE: haemotoxylin and eosin; IVDD: intervertebral disc degeneration; LAMP: lysosomal associated membrane protein; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFI: mean fluorescence intensity; MMP3: matrix metallopeptidase 3; MRI: magnetic resonance imaging; NP: nucleus pulposus; PG: Pfirrmann grade; PI: propidium iodide; RT-qPCR: reverse transcription-quantitative PCR; SOFG: safranin O fast green; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB.
Collapse
Affiliation(s)
- Sheng Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yiqiang Hu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weihua Xu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weijian Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bingjin Wang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xianlin Zeng
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zengwu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cao Yang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liming Xiong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xianyi Cai
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Orthopaedics, Hefeng Central Hospital, Enshi, China
| |
Collapse
|
|
5
|
Trogrlic A, Mrcela D, Budimir Mrsic D, Jukic I, Sardelic S, Tabain I, Hruskar Ž, Nonkovic D, Markic J, Pavicic Ivelja M. Clinical and Radiological Features of an Adenovirus Type 7 Outbreak in Split-Dalmatia County, Croatia, 2022-2023. Pathogens 2024; 13:1114. [PMID: 39770373 PMCID: PMC11678703 DOI: 10.3390/pathogens13121114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 01/11/2025] Open
Abstract
Human adenoviruses (HAdVs) are known to be highly contagious pathogens. They are commonly associated with mild respiratory infections in young children but can also cause severe life-threatening infections. Human adenovirus types 4 and 7 have frequently been reported to cause pneumonia in immunocompetent youths and adults. In this retrospective study, we analyzed the clinical, laboratory, radiological, and microbiological features, as well as the treatment and outcomes of an adenovirus outbreak in 185 patients who were admitted to the Emergency Unit of the Departments of Infectious Diseases and Pediatrics, University Hospital of Split, Croatia, between October 2022 and April 2023. An unusual increase in the frequency of adenovirus pneumonia was observed, especially in adults, followed by respiratory failure and complications such as pulmonary embolism. The most common chest X-ray findings were unilateral patchy opacity and unilateral reticulations (11.6%), followed by unilateral lobar pneumonia (7.1%). The predominant CT presentation was unilateral lobar pneumonia with multiple patchy ground glass opacities (23.5%) or lobar pneumonia with mixed opacities (17.6%). We found a low correlation between Brixia score and C-reactive protein in adults and no correlation in children. Adenovirus type 7 was almost exclusively isolated from patients with pneumonia. Most of our patients with severe or critical adenovirus pneumonia were immunocompetent adults without any medical history. So far, only a few studies have presented the radiological features of HAdV pneumonia, which generally did not reveal lobar pneumonia in a substantial percentage. Our research also demonstrated an unusual presentation of adenovirus infection complicated with pulmonary embolism, which has rarely been reported in previous studies. The aforementioned HAdV outbreak indicates the necessity for further research, especially in the context of effective antiviral therapy and infection prevention.
Collapse
Affiliation(s)
- Antea Trogrlic
- Department of Infectious Diseases, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia;
| | - Dina Mrcela
- Department of Pediatrics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.M.); (I.J.)
| | - Danijela Budimir Mrsic
- Department of Diagnostic and Interventional Radiology, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia;
- School of Medicine, University of Split, Soltanska 2a, 21000 Split, Croatia
| | - Ivana Jukic
- Department of Pediatrics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.M.); (I.J.)
| | - Sanda Sardelic
- Department of Microbiology and Parasitology, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia;
| | - Irena Tabain
- Croatian Institute of Public Health, Rockefellerova 7, 10000 Zagreb, Croatia; (I.T.); (Ž.H.)
| | - Željka Hruskar
- Croatian Institute of Public Health, Rockefellerova 7, 10000 Zagreb, Croatia; (I.T.); (Ž.H.)
| | - Diana Nonkovic
- Teaching Institute for Public Health of Split-Dalmatia County, Vukovarska 46, 21000 Split, Croatia;
- Department of Health Studies, University of Split, R. Boskovica 35, 21000 Split, Croatia
| | - Josko Markic
- Department of Pediatrics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (D.M.); (I.J.)
- School of Medicine, University of Split, Soltanska 2a, 21000 Split, Croatia
| | - Mirela Pavicic Ivelja
- Department of Infectious Diseases, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia;
- Department of Health Studies, University of Split, R. Boskovica 35, 21000 Split, Croatia
| |
Collapse
|
|
6
|
Daly SW, Chieng B, Araka S, Mboya J, Imali C, Swarthout JM, Njenga SM, Pickering AJ, Harris AR. Enteric Pathogens in Humans, Domesticated Animals, and Drinking Water in a Low-Income Urban Area of Nairobi, Kenya. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:21839-21849. [PMID: 39591504 PMCID: PMC11636211 DOI: 10.1021/acs.est.4c10041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/28/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024]
Abstract
To explore the sources of and associated risks with drinking water contamination in low-income, densely populated urban areas, we collected human feces, domesticated animal feces, and source and stored drinking water samples in Nairobi, Kenya in 2019; and analyzed them using microbial source tracking (MST) and enteric pathogen TaqMan Array Cards (TACs). We established host-pathogen relationships in this setting, including detecting Shigella and Norovirus─which are typically associated with humans─in dog feces. We evaluated stored and source drinking water quality using indicator Escherichia coli (E. coli), MST markers, and TACs, detecting pathogen targets in drinking water that were also detected in specific animal feces. This work highlights the need for further evaluation of host-pathogen relationships and the directionality of pathogen transmission to prevent the disease burden associated with unsafe drinking water and domestic animal ownership.
Collapse
Affiliation(s)
- Sean W. Daly
- Department
of Civil, Construction, and Environmental Engineering, North Carolina State University, Fitts-Woolard Hall, 915 Partners
Way, Rm 3250, Raleigh, North
Carolina 27695, United States
| | - Benard Chieng
- Kenya
Medical Research Institute, Nairobi 00100, Kenya
| | - Sylvie Araka
- Kenya
Medical Research Institute, Nairobi 00100, Kenya
| | - John Mboya
- Kenya
Medical Research Institute, Nairobi 00100, Kenya
- Department
of Civil and Environmental Engineering, University of California, Berkeley, Berkeley, California 94720, United States
| | | | - Jenna M. Swarthout
- Civil
and Environmental Engineering, Tufts University, Medford, Massachusetts 02155, United States
| | | | - Amy J. Pickering
- Department
of Civil and Environmental Engineering, University of California, Berkeley, Berkeley, California 94720, United States
- Chan
Zuckerberg
Biohub, San Francisco, California 94158, United States
| | - Angela R. Harris
- Department
of Civil, Construction, and Environmental Engineering, North Carolina State University, Fitts-Woolard Hall, 915 Partners
Way, Rm 3250, Raleigh, North
Carolina 27695, United States
| |
Collapse
|
|
7
|
Tarcsai KR, Bányai K, Bali K, Abbas AA, Kövesdi V, Ongrádi J. Feline Adenovirus Isolate Shows Silent Nucleotide Alterations, Alternative Receptor/Coreceptor Binding, High Resistance to Disinfectants and Antiviral Drugs, as Well as Immunomodulation. Animals (Basel) 2024; 14:3502. [PMID: 39682467 DOI: 10.3390/ani14233502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/27/2024] [Accepted: 11/28/2024] [Indexed: 12/18/2024] Open
Abstract
Adenovirus (AdV) infection has been rarely documented in cats and other felids. Partial sequences of the hexon and fiber genes of a Hungarian feline adenovirus isolate (FeAdV isolate) showed a close relationship to human AdV (HAdV) type C1. Further molecular and biological characterization is reported here. Whole-genome sequencing revealed two silent mutations in the genome of the FeAdV isolate compared to a HAdV-C1 reference strain (at positions 14,096 and 15,082). Competitive antibody binding to the Coxsackie-adenovirus receptor and αvβ3 and αvβ5 integrin coreceptors inhibited the binding of the FeAdV isolate in different cell lines, but residual infections suggested alternative entry routes. The FeAdV isolate was found to be more sensitive to heat, low pH and detergents, but more resistant to alkaline and free chlorine treatments, as well as to ribavirin, stavudine and cidofovir treatments, than other human AdV types. We observed a suppression of IL-10 and TGF-β1 production during the entire course of viral replication. This immunomodulation may restore intratumoral immunity; thus, the FeAdV isolate could serve as an alternative oncolytic vector. Collectively, our results support that the Hungarian FeAdV isolate is a variant of common HAdV-C1. The cohabitation of cats with humans might result in reverse zoonotic infection. Felids appear to be susceptible to persistent and productive adenovirus infection, but further studies are needed to better understand the clinical and epidemiological implications.
Collapse
Affiliation(s)
| | - Krisztián Bányai
- Pathogen Discovery Group, HUN-REN Veterinary Medical Research Institute, 1143 Budapest, Hungary
- Department of Pharmacology and Toxicology, University of Veterinary Medicine, 1078 Budapest, Hungary
- Szentágothai Research Centre, University of Pécs, 7622 Pécs, Hungary
- Department of Laboratory Medicine, Medical School, University of Pécs, 7622 Pécs, Hungary
| | - Krisztina Bali
- Pathogen Discovery Group, HUN-REN Veterinary Medical Research Institute, 1143 Budapest, Hungary
- Department of Microbiology and Infectious Diseases, University of Veterinary Medicine, 1078 Budapest, Hungary
| | | | - Valéria Kövesdi
- Department of Preventive Medicine and Public Health, Semmelweis University, 1085 Budapest, Hungary
| | - József Ongrádi
- Department of Preventive Medicine and Public Health, Semmelweis University, 1085 Budapest, Hungary
- Department of Transfusion Medicine, Semmelweis University, 1085 Budapest, Hungary
| |
Collapse
|
|
8
|
Walsh HA. Preterminal protein, the achilles heel of adenoviridae: Implications for adenoviral infections. World J Pharmacol 2024; 13:97723. [DOI: 10.5497/wjp.v13.i2.97723] [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: 06/13/2024] [Revised: 10/03/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Adenoviruses pose a serious health risk particularly in the absence of any clinically approved treatment. As adenoviral infections are quite frequent and recent outbreaks manifest more virulent variant strains, the need to develop an effective treatment remains a priority. The adenoviral protein, preterminal protein (pTP), is one of the key common products of the viral lifecycle as it is necessary to initiate viral replication and hence the infection process. This makes pTP a potential chemotherapeutic target in the search for and development of an effective treatment for adenoviral induced infections. Here we report, for the first time, that glycosylation of pTP in situ prevents binding to ssDNA in vitro.
AIM To explore whether specific structural tailoring of the adenoviral protein pTP, imparts the potential to scupper the viral replication process.
METHODS All chemicals used were of reagent grade. Overexpression of pTP was achieved using the ‘BAC to BAC’ expression system. The presence and relative concentration of the protein was determined throughout the incubation period by the Bradford assay. The pTP was identified by MALDI-TOFF and sodium dodecyl sulphate polyacrylamide gel electrophoresis. For the removal of the aminosugar, a deglycosylase enzyme kit from PROZYME was used. Purification of cloned pTP (6xHis) was done with a ssDNA cellulose column followed by a Ni-NTA column. His-tags were excised with the Tobacco etch virus protease. Protein fractionation was performed with a fraction collector coupled to a UV detector (280 nm) from Pharmacia.
RESULTS The pTP overexpressed in insect cells (Spodoptera frugiperda) (> 96 hours), is unable to bind to ssDNA in vitro. Treatment of this unbound protein with a deglycosidase enzyme that is specific for the removal of truncated unsubstituted O-linked Galβ(1-3)GalNAc-α1 disaccharides bound to Thr or Ser in a glycoprotein, restores binding to ssDNA. Data is presented as a linegraph for both the glycosylated and the deglycosylated proteins. Each point represents the mean of triplicate experiments (from different batches). Means and standard deviation were calculated and plotted on a line graph (with error bars).
CONCLUSION The finding that glycosylation of cloned pTP in situ prevents binding to ssDNA in vitro could aid in the development of an effective treatment of adenoviral infections and/or as an adjunct to complement other anti-adenoviral chemotherapeutic strategies.
Collapse
Affiliation(s)
- Harold A Walsh
- Faculty of Pharmacy, Division of Pharmacology, Rhodes University, Grahamstown 6139, Eastern Cape, South Africa
| |
Collapse
|
|
9
|
Gomez-Gonzalez A, Burkhardt P, Bauer M, Suomalainen M, Mateos JM, Loehr MO, Luedtke NW, Greber UF. Stepwise virus assembly in the cell nucleus revealed by spatiotemporal click chemistry of DNA replication. SCIENCE ADVANCES 2024; 10:eadq7483. [PMID: 39454009 PMCID: PMC11506174 DOI: 10.1126/sciadv.adq7483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 09/23/2024] [Indexed: 10/27/2024]
Abstract
Biomolecular assemblies are fundamental to life and viral disease. The spatiotemporal coordination of viral replication and assembly is largely unknown. Here, we developed a dual-color click chemistry procedure for imaging adenovirus DNA (vDNA) replication in the cell nucleus. Late- but not early-replicated vDNA was packaged into virions. Early-replicated vDNA segregated from the viral replication compartment (VRC). Single object tracking, superresolution microscopy, fluorescence recovery after photobleaching, and correlative light-electron microscopy revealed a stepwise assembly program involving vDNA and capsid intermediates. Depending on replication and the scaffolding protein 52K, late-replicated vDNA with rapidly exchanging green fluorescent protein-tagged capsid linchpin protein V and incomplete virions emerged from the VRC periphery. These nanogel-like puncta exhibited restricted movements and were located with the capsid proteins hexon, VI, and virions in the nuclear periphery, suggestive of sites for virion formation. Our findings identify VRC dynamics and assembly intermediates, essential for stepwise productive adenovirus morphogenesis.
Collapse
Affiliation(s)
| | - Patricia Burkhardt
- Department of Molecular Life Sciences, University of Zurich (UZH), Zurich, Switzerland
| | - Michael Bauer
- Department of Molecular Life Sciences, University of Zurich (UZH), Zurich, Switzerland
| | - Maarit Suomalainen
- Department of Molecular Life Sciences, University of Zurich (UZH), Zurich, Switzerland
| | - José María Mateos
- Center for Microscopy and Image Analyses, University of Zurich (UZH), Zurich, Switzerland
| | - Morten O. Loehr
- Department of Chemistry, McGill University, Montréal, QC, Canada
| | | | - Urs F. Greber
- Department of Molecular Life Sciences, University of Zurich (UZH), Zurich, Switzerland
| |
Collapse
|
|
10
|
Zhou H, Chen D, Ru X, Shao Q, Chen S, Liu R, Gu R, Shen J, Ye Q, Cheng D. Epidemiological and clinical characteristics of adenovirus-associated respiratory tract infection in children in Hangzhou, China, 2019-2024. J Med Virol 2024; 96:e29957. [PMID: 39370869 DOI: 10.1002/jmv.29957] [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: 08/17/2024] [Revised: 09/16/2024] [Accepted: 09/26/2024] [Indexed: 10/08/2024]
Abstract
This study aimed to assess the impact of COVID-19 on the prevalence of adenovirus (AdV) infection in children. This study retrospectively analyzed the changes in the epidemiological and clinical features of AdV-associated respiratory infections in children in Hangzhou, China, between January 2019 and July 2024. A total of 771 316 samples were included in the study, and the positive rate was 6.10% (47 050/771 316). Among them, the positive rate of AdV infection was highest in 2019, reaching 11.29% (26 929/238 333), while the positive rates in the remaining years were between 2% and 9%. In terms of seasonal epidemic characteristics, the summer of 2019 was the peak of AdV incidence, with the positive rate peaking at around 16.95% (7275/45 268), followed by a gradual decline and a low-level epidemic in winter, with a positive rate of 8.79% (8094/92 060). However, during the period 2020-2024, the AdV epidemic season did not show any significant regularity. Gender analysis revealed that the positive rate of male patients was generally greater than that of female patients. In different age groups, the population susceptible to AdV changed before and after the epidemic. In the early and middle stages of the COVID-19 epidemic, the susceptible population was mainly 2-5 years old, whereas in the later stages of the epidemic, the susceptible population was 5-18 years old. In addition, the main clinical symptoms of AdV-positive children from 2019-2024 were respiratory tract symptoms and fever. In summary, the COVID-19 epidemic has had a certain impact on the prevalence of AdV. These findings provide an important basis and reference for the prevention and diagnosis of AdV, especially in the context of increasing age- and gender-specific public health strategies.
Collapse
Affiliation(s)
- Haiyun Zhou
- Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Danlei Chen
- Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuanwen Ru
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qingyi Shao
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Simiao Chen
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ruiying Liu
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Rui Gu
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiayi Shen
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qing Ye
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dongqing Cheng
- Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| |
Collapse
|
|
11
|
Rahman M, Cronmiller S, Ernest J, Nguyen J, Zong D, Davis R, Rawa A, Thomas M, Al Mosharrafa R, Shanjana Y, Islam M. Mutated Adenovirus Attacks in West Bengal, India: Risk Evaluation of Multi-Country Outbreaks and Mitigation Strategies. Nurs Open 2024; 11:e70065. [PMID: 39428960 PMCID: PMC11491688 DOI: 10.1002/nop2.70065] [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: 06/13/2023] [Revised: 06/14/2024] [Accepted: 09/13/2024] [Indexed: 10/22/2024] Open
Abstract
AIM The human adenovirus (HAdV) is beginning to spread rapidly in children through human, surface and animal vectors. Around 12,000 cases were recognised in 2022 in West Bengal and a shocking number of cases arose throughout India and in other under-developed areas. This is going to be a big threat to public health since no vaccine, awareness or protocol policies were introduced. Early detection, immediate isolation and proper policy developments are the key factors in overcoming the situation. Therefore, we performed this rapid review and discussed probable mitigation strategies, updated research on vaccine development, and treatment strategies to control the outbreaks of mutated HAdV. DESIGN This is a narrative review of publicly available information. METHODS Here, we extracted updated information and data using the terms HAdV outbreaks, mutations, species, risks and prevention from Google Scholar and PubMed. We considered relevant articles that have discussed prevention strategies, ongoing research, and antiviral drugs for managing HAdV outbreaks. RESULTS Early detection from throat swabs, isolation and symptomatic treatments are required to minimise viral infections. A massive test needs to be performed to find the affected people. The cases should be immediately isolated. It is recommended to treat high-touch surfaces with heat- or bleach-containing cleaners to prevent the spread of infection. Oxygen support and many broad-spectrum antivirals have been used to treat HAdV. Several studies showed antibody neutralisation and interactions between the natural killer cell receptor KIR3DS1 and HLA-F in infected cells, indicating possible therapeutic options in the future. HAdV-4 and HAdV-7 vaccines have been limitedly approved for administration to military personnel. CONCLUSION Isolation, certain safety measures, broad-spectrum antiviral drugs and further research on new vaccines could be useful to prevent this virus from producing a worldwide pandemic. Also, the authorities should ensure the proper therapeutic interventions and nursing care facilities for the infected children. PATIENT OR PUBLIC CONTRIBUTION Patient or public contribution was not relevant to our work.
Collapse
Affiliation(s)
| | - Sydney Cronmiller
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Julianne Ernest
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Jonah Nguyen
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Donovan Zong
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Rob Davis
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Amanda Rawa
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Marie Roke Thomas
- Nesbitt School of Pharmacy Wilkes UniversityWilkes‐BarrePennsylvaniaUSA
| | - Rana Al Mosharrafa
- Department of Business Administration, Faculty of Business StudiesPrime UniversityDhakaBangladesh
| | - Yeasna Shanjana
- Department of Environmental SciencesNorth South University, BashundharaDhakaBangladesh
| | | |
Collapse
|
|
12
|
Graves D, Akkerman N, Fulham L, Helwer R, Pelka P. Molecular insights into type I interferon suppression and enhanced pathogenicity by species B human adenoviruses B7 and B14. mBio 2024; 15:e0103824. [PMID: 38940561 PMCID: PMC11323573 DOI: 10.1128/mbio.01038-24] [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: 04/05/2024] [Accepted: 05/22/2024] [Indexed: 06/29/2024] Open
Abstract
Human adenoviruses (HAdVs) are small DNA viruses that generally cause mild disease. Certain strains, particularly those belonging to species B HAdVs, can cause severe pneumonia and have a relatively high mortality rate. Little is known about the molecular aspects of how these highly pathogenic species affect the infected cell and how they suppress innate immunity. The present study provides molecular insights into how species B adenoviruses suppress the interferon signaling pathway. Our study shows that these viruses, unlike HAdV-C2, are resistant to type I interferon. This resistance likely arises due to the highly efficient suppression of interferon-stimulated gene expression. Unlike in HAdV-C2, HAdV-B7 and B14 sequester STAT2 and RNA polymerase II from interferon-stimulated gene promoters in infected cells. This results in suppressed interferon- stimulated gene activation. In addition, we show that RuvBL1 and RuvBL2, cofactors important for RNA polymerase II recruitment to promoters and interferon-stimulated gene activation, are redirected to the cytoplasm forming high molecular weight complexes that, likely, are unable to associate with chromatin. Proteomic analysis also identified key differences in the way these viruses affect the host cell, providing insights into species B-associated high pathogenicity. Curiously, we observed that at the level of protein expression changes to the infected cell, HAdV-C2 and B7 were more similar than those of the same species, B7 and B14. Collectively, our study represents the first such study of innate immune suppression by the highly pathogenic HAdV-B7 and B14, laying an important foundation for future investigations.IMPORTANCEHuman adenoviruses form a large family of double-stranded DNA viruses known for a variety of usually mild diseases. Certain strains of human adenovirus cause severe pneumonia leading to much higher mortality and morbidity than most other strains. The reasons for this enhanced pathogenicity are unknown. Our study provides a molecular investigation of how these highly pathogenic strains might inactivate the interferon signaling pathway, highlighting the lack of sensitivity of these viruses to type I interferon in general while providing a global picture of how viral changes in cellular proteins drive worse disease outcomes.
Collapse
Affiliation(s)
- Drayson Graves
- Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Nikolas Akkerman
- Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Lauren Fulham
- Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Rafe Helwer
- Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Peter Pelka
- Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada
| |
Collapse
|
|
13
|
Ferreira FDG, Carlon P, Fongaro G, Magri ME. Recycling composted human feces as biofertilizer for crop production: Assessment of soil and lettuce plant tissue contamination by Escherichia coli and human adenovirus. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 928:172375. [PMID: 38604372 DOI: 10.1016/j.scitotenv.2024.172375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 04/13/2024]
Abstract
Using waste from sewage systems, particularly human excreta, could save resources and increase soil fertility, contributing to nutrient management. However, because of the pathogenic content in human feces, this resource can pose health risks to farmers and consumers. Therefore, this work analyzed the behavior of the microorganisms: Escherichia coli ATCC13706 and human adenovirus (HAdV-2) in the soil and the internal part of the plant tissue during the vegetative stage after applying spiked composted human feces as biofertilizer. In a greenhouse, we simulated the application of the biofertilizer in lettuce cultivation by spiking three concentrations of E. coli (6.58, 7.31, and 8.01 log10 CFU.g-1) and HAdV-2 (3.81, 3.97, and 5.92 log10 PFU.g-1). As a result, we achieved faster decay in soil at higher concentrations of E. coli. We estimated linear decay rates of -0.07279, -0.09092, and -0.115 days, corresponding to T90s of 13.7, 11.0, and 8.6 days from higher to smaller concentrations of E. coli, respectively. The estimated periods for the inactivation of 4 logarithmic units of E. coli bacteria in soil are longer than the cultivation period of lettuce for all concentrations studied. Concerning the bacterial contamination in plants, we found E. coli in the internal part of the leaves at the highest concentration tested during the first three weeks of the experiment. Furthermore, HAdV-2 was found in roots at a stable concentration of 2-2.3 log10 PFU.g-1 in five of the six samples analyzed. Therefore, bacterial infection could pose a risk, even if fresh greens are washed before consumption, especially for short-term cultures. Regarding viral infection, a positive result in the roots after disinfection may pose a risk to root and tubercule vegetables. These discoveries highlight the importance of conducting comprehensive evaluations of hygiene practices in incorporating organic amendments in crops, explicitly aiming to minimize the risk of post-contamination.
Collapse
Affiliation(s)
- Fernanda Daniela Goncalves Ferreira
- Laboratory of Resource Recovery in Sanitation Systems Group - RReSSa, Department of Environmental Engineering, Federal University of Santa Catarina, Technological Center, Florianopolis 88040-610, Santa Catarina, Brazil.
| | - Priscila Carlon
- Laboratory of Resource Recovery in Sanitation Systems Group - RReSSa, Department of Environmental Engineering, Federal University of Santa Catarina, Technological Center, Florianopolis 88040-610, Santa Catarina, Brazil
| | - Gislaine Fongaro
- Laboratory of Applied Virology, Department of Microbiology, Immunology, and Parasitology, Federal University of Santa Catarina, Biological Sciences Center, Florianopolis 88040-610, Santa Catarina, Brazil
| | - Maria Elisa Magri
- Laboratory of Resource Recovery in Sanitation Systems Group - RReSSa, Department of Environmental Engineering, Federal University of Santa Catarina, Technological Center, Florianopolis 88040-610, Santa Catarina, Brazil
| |
Collapse
|
|
14
|
Bachus S, Akkerman N, Fulham L, Graves D, Helwer R, Rempel J, Pelka P. ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair. Nucleic Acids Res 2024; 52:5658-5675. [PMID: 38520408 PMCID: PMC11162773 DOI: 10.1093/nar/gkae208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 03/05/2024] [Accepted: 03/11/2024] [Indexed: 03/25/2024] Open
Abstract
Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as a significant player in transcription and the DNA damage response pathway. Transcriptional effects induced by ARGLU1 occur via enhancement of promoter-proximal RNA polymerase II pausing, likely by inhibiting the interaction between JMJD6 and BRD4. When overexpressed, ARGLU1 increases the growth rate of cancer cells, while its knockdown leads to growth arrest. Significantly, overexpression of ARGLU1 increased cancer cell resistance to genotoxic drugs and promoted DNA damage repair. These results identify new roles for ARGLU1 in cancer cell survival and the DNA damage repair pathway, with potential clinical implications for chemotherapy resistance.
Collapse
Affiliation(s)
- Scott Bachus
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| | - Nikolas Akkerman
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| | - Lauren Fulham
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| | - Drayson Graves
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| | - Rafe Helwer
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| | - Jordan Rempel
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| | - Peter Pelka
- Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
| |
Collapse
|
|
15
|
Abstract
PURPOSE OF REVIEW Lower respiratory tract infections (LRTIs) are an important cause of child morbidity and mortality globally, especially in children under the age of 5 years in Africa. Respiratory viruses, including human adenoviruses (HAdVs), are common causes of LRTIs in children. This review aims to shed light on the epidemiology, clinical manifestations, sequelae, and treatment options specific to adenovirus respiratory infections in African children. RECENT FINDINGS Recent evidence has challenged the perception that adenovirus is a negligible cause of LRTIs. Studies show HAdV emerging as the third most common viral pathogen in fatal pneumonias among under-5 children in low-income and middle-income African countries, contributing to 5.5% of all pneumonia deaths and ranking second in hospital-associated viral pneumonia deaths. Predominant HAdV serotypes associated with disease differ by country and region, and have changed over time. Risk factors for increased disease severity and long-term respiratory sequelae in previously healthy African children with HAdV LRTIs are not well established. SUMMARY Although respiratory viruses, including HAdV, are recognized contributors to LRTIs, the prevalence and impact of adenovirus infections have been under-recognized and understated. Available data suggests that African children, particularly those under 5 years old, are at risk of severe sequelae from respiratory HAdV infections. Long-term sequelae, including bronchiectasis and postinfectious bronchiolitis obliterans, further underscore the significant impact of HAdV infections. However, the scarcity of comprehensive data hampers our understanding of the extent of the impact of HAdV infections on child lung health in Africa. We recommend scaled-up HAdV surveillance, ensuring its consistent inclusion in population-level LRTI assessments, and expanded and equitable access to diagnostics for early recognition of African children at risk of developing chronic sequelae and death. Enhanced understanding of adenovirus epidemiology and clinical outcomes and the availability of therapeutic options are essential for informed public health strategies and clinical care.
Collapse
Affiliation(s)
- Marieke M. van der Zalm
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Nadia A. Sam-Agudu
- International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria
- Department of Pediatrics and Child Health, University of Cape Coast School of Medical Sciences, Cape Coast, Ghana
- Global Pediatrics program and Division of Infectious Diseases, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Lilly M. Verhagen
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Department of Pediatric Infectious Diseases and Immunology, Amalia Children's Hospital
- Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| |
Collapse
|
|
16
|
Takuissu GR, Kenmoe S, Ebogo-Belobo JT, Kengne-Ndé C, Mbaga DS, Bowo-Ngandji A, Ondigui Ndzie JL, Kenfack-Momo R, Tchatchouang S, Kenfack-Zanguim J, Lontuo Fogang R, Zeuko'o Menkem E, Kame-Ngasse GI, Magoudjou-Pekam JN, Suffredini E, Veneri C, Mancini P, Bonanno Ferraro G, Iaconelli M, Verani M, Federigi I, Carducci A, La Rosa G. Exploring adenovirus in water environments: a systematic review and meta-analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:2504-2516. [PMID: 37678554 DOI: 10.1080/09603123.2023.2255559] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 09/01/2023] [Indexed: 09/09/2023]
Abstract
Adenoviruses (AdVs) have a significant impact in both medical and environmental contexts. The objective of this study was to investigate the prevalence of AdV in different water types, such as untreated and treated wastewater, surface water, groundwater, drinking water, and other water matrices. A total of 239 articles were included in this meta-analysis. Adenoviruses were detected in various waters worldwide. The overall prevalence in water was found to be 59.2%, with the highest prevalence in untreated wastewater (83.1%) and treated wastewater (75.3%), followed by "other water matrices" (53.4%), surface water (49.5%) drinking water (22.7%), and groundwater (18.5%). Most of the studies did not assess the viability of the viruses, leading to weak links between water contamination and risk. Both human and animal AdV were found in water environments. The findings suggest that water, including drinking water, could be a significant route of AdV transmission in both developed and developing economies.
Collapse
Affiliation(s)
- G R Takuissu
- Centre for Food, Food Security and Nutrition Research, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | - S Kenmoe
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - J T Ebogo-Belobo
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | - C Kengne-Ndé
- Epidemiological Surveillance, Evaluation and Research Unit, National AIDS Control Committee, Douala, Cameroon
| | - D S Mbaga
- Department of Microbiology, The University of Yaounde I, Yaounde, Cameroon
| | - A Bowo-Ngandji
- Department of Microbiology, The University of Yaounde I, Yaounde, Cameroon
| | - J L Ondigui Ndzie
- Department of Microbiology, The University of Yaounde I, Yaounde, Cameroon
| | - R Kenfack-Momo
- Department of Biochemistry, The University of Yaounde I, Yaounde, Cameroon
| | - S Tchatchouang
- Scientific Direction, Centre Pasteur du Cameroun, Yaounde, Cameroon
| | - J Kenfack-Zanguim
- Department of Biochemistry, The University of Yaounde I, Yaounde, Cameroon
| | - R Lontuo Fogang
- Department of Animal Biology, University of Dschang, Dschang, Cameroon
| | - E Zeuko'o Menkem
- Department of Biomedical Sciences, University of Buea, Buea, Cameroon
| | - G I Kame-Ngasse
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | | | - E Suffredini
- Department of Food Safety, Nutrition and Veterinary public health, Istituto Superiore di Sanità, Rome, Italy
| | - C Veneri
- National Center for Water Safety (CeNSia), Istituto Superiore di Sanità, Rome, Italy
| | - P Mancini
- National Center for Water Safety (CeNSia), Istituto Superiore di Sanità, Rome, Italy
| | - G Bonanno Ferraro
- National Center for Water Safety (CeNSia), Istituto Superiore di Sanità, Rome, Italy
| | - M Iaconelli
- National Center for Water Safety (CeNSia), Istituto Superiore di Sanità, Rome, Italy
| | - M Verani
- Hygiene and Environmental Virology Laboratory, Department of Biology, University of Pisa, Pisa, Italy
| | - I Federigi
- Hygiene and Environmental Virology Laboratory, Department of Biology, University of Pisa, Pisa, Italy
| | - A Carducci
- Hygiene and Environmental Virology Laboratory, Department of Biology, University of Pisa, Pisa, Italy
| | - G La Rosa
- National Center for Water Safety (CeNSia), Istituto Superiore di Sanità, Rome, Italy
| |
Collapse
|
|
17
|
Wang S, Zou X, Fu J, Deng F, Yu H, Fan H, Dai Q, Shang Q, Xu K, Bao C. Genotypes and Phylogenetic Analysis of Human Adenovirus in Hospitalized Pneumonia and Influenza-Like Illness Patients in Jiangsu Province, China (2013-2021). Infect Drug Resist 2024; 17:2199-2211. [PMID: 38835492 PMCID: PMC11149707 DOI: 10.2147/idr.s456961] [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: 12/27/2023] [Accepted: 05/22/2024] [Indexed: 06/06/2024] Open
Abstract
Background Human adenovirus (HAdV) is common pathogens that cause various respiratory diseases. The genetic diversity of viruses caused by recombination is considered to be the main source of emerging outbreaks. The aim of this study is to explore the evolutionary relationship and recombination events of HAdV genome in respiratory tract infections in Jiangsu Province. Methods Whole-genome sequencing (WGS) technology was used to sequence 66 patients with HAdV infection (37 patients with influenza-like illness (ILI) and 29 hospitalized patients with pneumonia) from Jiangsu Province. Epidemiological analysis was performed on hospitalized pneumonia and ILI patients infected with HAdV. Subsequently, phylogenetic, recombination, and nucleotide and amino acid identity analyses were performed. Results Epidemiological analysis of patients undergoing WGS showed that 75.7% of ILI patients were infected with the HAdVB strain and 69.0% of hospitalized pneumonia patients were infected with the HAdVC strain. Moreover, the hospitalized pneumonia and ILI patients infected with HAdV were different in region and time. The strains of HAdVB3 and HAdVB7 genotypes were mainly infected in 2015 and 2017, and the strains of HAdVC1 and HAdVC2 genotypes were mainly infected in 2020. The results of histogram analysis showed that the HAdV strain mainly infected children under 5 years old. In addition, 36 novel recombinant strains were identified. The discovery of these recombinant strains may contribute to understanding the epidemiology of HAdV and research on related vaccines. Furthermore, the percentage of nucleotide and amino acid identities revealed a high level of genetic conservation within isolates from HAdVB3, HAdVB7, HAdVC1, HAdVC2 and HAdVC5 genotypes. Conclusion The WGS analysis reveals the evolutionary relationships and recombination events of HAdV strains in Jiangsu Province, which is helpful to deepen the understanding of HAdV epidemiology and evolution. In addition, it provides a basis for the formulation of public health strategies in Jiangsu Province.
Collapse
Affiliation(s)
- Shenjiao Wang
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
- Ili Kazakh Autonomous Prefecture Center for Disease Control and Prevention, Ili, Xinjiang, People's Republic of China
| | - Xin Zou
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China
- Chongqing Key Laboratory of Viral Infectious Diseases, Chongqing, People's Republic of China
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China
| | - Jianguang Fu
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
| | - Fei Deng
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
| | - Huiyan Yu
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
| | - Huan Fan
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
| | - Qigang Dai
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
| | - Qingxiang Shang
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China
| | - Ke Xu
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
| | - Changjun Bao
- Acute Infectious Disease Control and Prevention Institute, Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing, Jiangsu Province, People's Republic of China
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China
| |
Collapse
|
|
18
|
King CR, Dodge MJ, MacNeil KM, Tessier TM, Mymryk JS, Mehle A. Expanding the adenovirus toolbox: reporter viruses for studying the dynamics of human adenovirus replication. J Virol 2024; 98:e0020724. [PMID: 38639487 PMCID: PMC11092356 DOI: 10.1128/jvi.00207-24] [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: 01/30/2024] [Accepted: 03/21/2024] [Indexed: 04/20/2024] Open
Abstract
To streamline standard virological assays, we developed a suite of nine fluorescent or bioluminescent replication competent human species C5 adenovirus reporter viruses that mimic their parental wild-type counterpart. These reporter viruses provide a rapid and quantitative readout of various aspects of viral infection and replication based on EGFP, mCherry, or NanoLuc measurement. Moreover, they permit real-time non-invasive measures of viral load, replication dynamics, and infection kinetics over the entire course of infection, allowing measurements that were not previously possible. This suite of replication competent reporter viruses increases the ease, speed, and adaptability of standard assays and has the potential to accelerate multiple areas of human adenovirus research.IMPORTANCEIn this work, we developed a versatile toolbox of nine HAdV-C5 reporter viruses and validated their functions in cell culture. These reporter viruses provide a rapid and quantitative readout of various aspects of viral infection and replication based on EGFP, mCherry, or NanoLuc measurement. The utility of these reporter viruses could also be extended for use in 3D cell culture, organoids, live cell imaging, or animal models, and provides a conceptual framework for the development of new reporter viruses representing other clinically relevant HAdV species.
Collapse
Affiliation(s)
- Cason R. King
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Mackenzie J. Dodge
- Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
| | - Katelyn M. MacNeil
- Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
| | - Tanner M. Tessier
- Division of Protective Immunity, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Joe S. Mymryk
- Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
- Department of Oncology, University of Western Ontario, London, Ontario, Canada
- Department of Otolaryngology, University of Western Ontario, London, Ontario, Canada
- London Regional Cancer Program, Lawson Health Research Institute, London, Ontario, Canada
| | - Andrew Mehle
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| |
Collapse
|
|
19
|
Portero V, Deng S, Boink GJJ, Zhang GQ, de Vries A, Pijnappels DA. Optoelectronic control of cardiac rhythm: Toward shock-free ambulatory cardioversion of atrial fibrillation. J Intern Med 2024; 295:126-145. [PMID: 37964404 DOI: 10.1111/joim.13744] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2023]
Abstract
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, progressive in nature, and known to have a negative impact on mortality, morbidity, and quality of life. Patients requiring acute termination of AF to restore sinus rhythm are subjected to electrical cardioversion, which requires sedation and therefore hospitalization due to pain resulting from the electrical shocks. However, considering the progressive nature of AF and its detrimental effects, there is a clear need for acute out-of-hospital (i.e., ambulatory) cardioversion of AF. In the search for shock-free cardioversion methods to realize such ambulatory therapy, a method referred to as optogenetics has been put forward. Optogenetics enables optical control over the electrical activity of cardiomyocytes by targeted expression of light-activated ion channels or pumps and may therefore serve as a means for cardioversion. First proof-of-principle for such light-induced cardioversion came from in vitro studies, proving optogenetic AF termination to be very effective. Later, these results were confirmed in various rodent models of AF using different transgenes, illumination methods, and protocols, whereas computational studies in the human heart provided additional translational insight. Based on these results and fueled by recent advances in molecular biology, gene therapy, and optoelectronic engineering, a basis is now being formed to explore clinical translations of optoelectronic control of cardiac rhythm. In this review, we discuss the current literature regarding optogenetic cardioversion of AF to restore normal rhythm in a shock-free manner. Moreover, key translational steps will be discussed, both from a biological and technological point of view, to outline a path toward realizing acute shock-free ambulatory termination of AF.
Collapse
Affiliation(s)
- Vincent Portero
- Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Shanliang Deng
- Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
- Department of Microelectronics, Delft University of Technology, Delft, The Netherlands
| | - Gerard J J Boink
- Department of Medical Biology, Department of Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Guo Qi Zhang
- Department of Microelectronics, Delft University of Technology, Delft, The Netherlands
| | - Antoine de Vries
- Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - Daniël A Pijnappels
- Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| |
Collapse
|
|
20
|
Lian X, Zhao X, Zhong J, Zhang C, Chu Y, Wang Y, Lu S, Wang Z. A New HEK293 Cell with CR2 Region of E1A Gene Deletion Prevents the Emergence of Replication-Competent Adenovirus. Cancers (Basel) 2023; 15:5713. [PMID: 38136259 PMCID: PMC10742158 DOI: 10.3390/cancers15245713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 11/23/2023] [Accepted: 11/29/2023] [Indexed: 12/24/2023] Open
Abstract
PURPOSE To eliminate the contaminants of Replication-Competent Adenovirus (RCA) during high titer recombinant oncolytic adenovirus production. METHODS At first, we detected E1A copy numbers of different sources of 293 cells using Q-PCR, and we screened a subclone JH293-C21 of the JH293 cell line (purchased from ATCC) with lower early region 1A (E1A) copy numbers and higher adenovirus production ability. Then, we deleted the conserved region (CR)2 of the E1A gene in this subclone using the CRISPR-Cas9 system and obtained a stable cell clone JH293-C21-C14 with lower E1A expression, but the RCA formation had no significant reduction. Then, we further deleted the CR2 of JH293-C21-C14 cells with the CRISPR-Cas9 system and obtained a strain of cells named JH293-C21-C14-C28. Finally, we detected the capacity for cell proliferation, adenovirus production, and RCA formation in the production of recombinant adenovirus. RESULTS The JH293-C21-C14-C28 cells had a similar cell proliferation ability and human adenovirus production as JH293-C21 cells. Most importantly, RCA production in JH293-C21-C14-C28 cells was lower than in JH293-C21 cells. CONCLUSION Human adenovirus producer cell clone JH293-C21-C14-C28 with CR2 deletion can effectively prevent the RCA production of replication-competent oncolytic adenovirus; this will provide significant advantages in utility and safety in gene therapy.
Collapse
Affiliation(s)
- Xueqi Lian
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| | - Xiaoyan Zhao
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| | - Jingjing Zhong
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| | - Chenglin Zhang
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| | - Yongchao Chu
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| | - Yaohe Wang
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
- Centre for Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
| | - Shuangshuang Lu
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| | - Zhimin Wang
- National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China; (X.L.); (X.Z.); (J.Z.); (C.Z.); (Y.C.); (Y.W.)
| |
Collapse
|
|
21
|
Trivedi PD, Byrne BJ, Corti M. Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines. Viruses 2023; 15:2378. [PMID: 38140619 PMCID: PMC10747483 DOI: 10.3390/v15122378] [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: 10/21/2023] [Revised: 11/27/2023] [Accepted: 11/29/2023] [Indexed: 12/24/2023] Open
Abstract
Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy by altering the wild-type virus and making it replication-defective; specific viral genes can be removed and replaced with a segment that holds a therapeutic gene, and this vector can be used as delivery vehicle for tissue specific gene delivery. Modified conditionally replicative-oncolytic adenoviruses target tumors exclusively and have been studied in clinical trials extensively. This comprehensive review seeks to offer a summary of adenovirus vectors, exploring their characteristics, genetic enhancements, and diverse applications in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing cancer therapy and the latest breakthroughs in vaccine clinical trials for various diseases. Additionally, we tackle current challenges and future avenues for optimizing adenovirus vectors, promising to open new frontiers in the fields of cell and gene therapies.
Collapse
Affiliation(s)
| | | | - Manuela Corti
- Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA; (P.D.T.); (B.J.B.)
| |
Collapse
|
|
22
|
Li M, Li J, Kang L, Gong C, Luo M, Wang X, Guan X, Tong Y, Huang F. Genome sequencing reveals molecular epidemiological characteristics and new recombinations of adenovirus in Beijing, China, 2014-2019. J Med Virol 2023; 95:e29284. [PMID: 38087446 DOI: 10.1002/jmv.29284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/13/2023] [Accepted: 11/19/2023] [Indexed: 12/18/2023]
Abstract
To investigate the molecular epidemiological characteristics and genetic variations of human adenovirus (HAdV) in acute respiratory tract infections in Beijing. Whole-genome sequencing and phylogenetic analyses were performed for 83 strains of HAdV with different types in Beijing from 2014 to 2019. The clinical characteristics of HAdV infection were analyzed statistically. HAdV-B was divided into four genotypes, including B3 (n = 11), B7 (n = 13), B14 (n = 4), and B55 (n = 2). HAdV-C was divided into three genotypes, including C1 (n = 14), C2 (n = 13), and C5 (n = 10). In HAdV-C, nine recombinant adenovirus strains were identified in type 1, and seven recombinant strains were found in type 2. In type 1, we found three newly emerged intraspecific recombinant strains (A47, A48, and A52) collected in 2017, 2018, and 2019, respectively. In addition, the previously reported recombinant strains of HAdV-C1 showed more severe disease than other strains of HAdV-C, causing severe community-acquired pneumonia in both the elderly and children. Continuous population-wide molecular epidemiological surveillance of HAdV is essential for the prevention and control of respiratory infectious diseases.
Collapse
Affiliation(s)
- Maozhong Li
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China
| | - Jing Li
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Lu Kang
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China
| | - Cheng Gong
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China
| | - Ming Luo
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
| | - Xue Wang
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
| | - Xuejiao Guan
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
| | - Yigang Tong
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Fang Huang
- Beijing Center for Disease Control and Prevention/Beijing Academy for Preventive Medicine/Beijing Institute of Tuberculosis Control Research and Prevention, Institute for immunization and prevention, Beijing, China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China
- College of Public Health, Capital Medical University, Beijing, China
| |
Collapse
|
|
23
|
Mazboudi R, Mulhall Maasz H, Resch MD, Wen K, Gottlieb P, Alimova A, Khayat R, Collins ND, Kuschner RA, Galarza JM. A recombinant virus-like particle vaccine against adenovirus-7 induces a potent humoral response. NPJ Vaccines 2023; 8:155. [PMID: 37821505 PMCID: PMC10567840 DOI: 10.1038/s41541-023-00754-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 10/02/2023] [Indexed: 10/13/2023] Open
Abstract
Adenoviruses (AdVs) cause infections in humans that range from mild to severe, and can cause outbreaks particularly in close contact settings. Several human AdV types have been identified, which can cause a wide array of clinical manifestations. AdV types 4 and 7 (AdV-4 and AdV-7), which are among the most commonly circulating types in the United States, are known to cause acute respiratory disease that can result in hospitalization and rarely, death. Currently, the only vaccines approved for use in humans are live virus vaccines against AdV-4 and AdV-7, though these vaccines are only authorized for use in U.S. military personnel. While they are efficacious, use of these live virus vaccines carries considerable risks of vaccine-associated viral shedding and recombination. Here, we present an alternative vaccination strategy against AdV-7 using the virus-like particle platform (AdVLP-7). We describe the production of stable recombinant AdVLP-7, and demonstrate that AdVLP-7 is structurally analogous to wild-type AdV-7 virions (WT AdV-7). Preclinical immunogenicity studies in mice show that AdVLP-7 elicits a potent humoral immune response, comparable to that observed in mice immunized with WT AdV-7. Specifically, AdVLP-7 induces high titers of antibodies against AdV-7-specific antigens that can effectively neutralize AdV-7.
Collapse
Affiliation(s)
- Ryan Mazboudi
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA
| | | | - Matthew D Resch
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA
| | - Ke Wen
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA
| | - Paul Gottlieb
- CUNY School of Medicine, The City College of New York, New York, NY, 10031, USA
| | - Aleksandra Alimova
- CUNY School of Medicine, The City College of New York, New York, NY, 10031, USA
| | - Reza Khayat
- Department of Chemistry and Biochemistry, The City College of New York, New York, NY, 10031, USA
| | - Natalie D Collins
- Viral Diseases Branch, Walter Reed Army Institute for Research, Silver Spring, MD, 20910, USA
| | - Robert A Kuschner
- Viral Diseases Branch, Walter Reed Army Institute for Research, Silver Spring, MD, 20910, USA
| | - Jose M Galarza
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA.
| |
Collapse
|
|
24
|
Sun N, Zhang J, Zhang C, Xie T, Zhang Z, Wang X, Li W, Zhang Y, Chen Z, Zheng J, Fang L, Wang G. Inhibition of human adenovirus replication by TRIM35-mediated degradation of E1A. J Virol 2023; 97:e0070023. [PMID: 37578239 PMCID: PMC10506487 DOI: 10.1128/jvi.00700-23] [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: 05/13/2023] [Accepted: 07/03/2023] [Indexed: 08/15/2023] Open
Abstract
Human adenovirus (HAdV) is ubiquitous in the human population, constituting a significant burden of global respiratory diseases. Children and individuals with low immunity are at risk of developing severe infections without approved antiviral treatment for HAdV. Our study demonstrated that TRIM35 inhibited HAdV-C5 early gene transcription, early protein expression, genome replication, and infectious virus progeny production. Furthermore, TRIM35 was found to inhibit HAdV replication by attenuating E1A expression. Mechanistically, TRIM35 interacts with and degrades E1A by promoting its K48-linked ubiquitination. Additionally, K253 and K285 are the key sites necessary for TRIM35 degradation. Moreover, an oncolytic adenovirus carrying shTRIM35 was constructed and observed to exhibit improved oncolysis in vivo, providing new ideas for clinical tumor treatment. Our results expand the broad antiviral activity of TRIM35 and mechanically support its application as a HAdV replication inhibitor. IMPORTANCE E1A is an essential human adenovirus (HAdV) protein responsible for the early replication of adenovirus while interacting with multiple host proteins. Understanding the interaction between HAdV E1A and TRIM35 helps identify effective antiviral therapeutic targets. The viral E1A protein is a crucial activator and regulator of viral transcription during the early infection stages. We first reported that TRIM35 interacts with E1A to resist adenovirus infection. Our study demonstrated that TRIM35 targets E1A to resist adenovirus, indicating the applicability of targeting virus-dependent host factors as a suitable antiviral strategy.
Collapse
Affiliation(s)
- Nan Sun
- Xuzhou Medical University, Xuzhou, China
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | | | - Chen Zhang
- Xuzhou Medical University, Xuzhou, China
| | - Tan Xie
- Xuzhou Medical University, Xuzhou, China
| | - Zeyu Zhang
- Xuzhou Medical University, Xuzhou, China
| | | | - Wanjing Li
- Xuzhou Medical University, Xuzhou, China
| | - Yi Zhang
- Xuzhou Medical University, Xuzhou, China
| | | | - Junnian Zheng
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Lin Fang
- Xuzhou Medical University, Xuzhou, China
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Gang Wang
- Xuzhou Medical University, Xuzhou, China
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| |
Collapse
|
|
25
|
Zhang J, Zhu Y, Zhou Y, Gao F, Qiu X, Li J, Yuan H, Jin W, Lin W. Pediatric adenovirus pneumonia: clinical practice and current treatment. Front Med (Lausanne) 2023; 10:1207568. [PMID: 37476615 PMCID: PMC10354292 DOI: 10.3389/fmed.2023.1207568] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 06/19/2023] [Indexed: 07/22/2023] Open
Abstract
Adenovirus pneumonia is common in pediatric upper respiratory tract infection, which is comparatively easy to develop into severe cases and has a high mortality rate with many influential sequelae. As for pathogenesis, adenoviruses can directly damage target cells and activate the immune response to varying degrees. Early clinical recognition depends on patients' symptoms and laboratory tests, including those under 2 years old, dyspnea with systemic toxic symptoms, atelectasis or emphysema in CT image, decreased leukocytes, and significantly increased C-reaction protein (CRP) and procalcitonin (PCT), indicating the possibility of severe cases. Until now, there is no specific drug for adenovirus pneumonia, so in clinical practice, current treatment comprises antiviral drugs, respiratory support and bronchoscopy, immunomodulatory therapy, and blood purification. Additionally, post-infectious bronchiolitis obliterans (PIBO), hemophagocytic syndrome, and death should be carefully noted. Independent risk factors associated with the development of PIBO are invasive mechanical ventilation, intravenous steroid use, duration of fever, and male gender. Meanwhile, hypoxemia, hypercapnia, invasive mechanical ventilation, and low serum albumin levels are related to death. Among these, viral load and serological identification are not only "gold standard" for adenovirus pneumonia, but are also related to the severity and prognosis. Here, we discuss the progress of pathogenesis, early recognition, therapy, and risk factors for poor outcomes regarding severe pediatric adenovirus pneumonia.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Wei Lin
- Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| |
Collapse
|
|
26
|
Hannestad U, Apostolou E, Sjögren P, Bragée B, Polo O, Bertilson BC, Rosén A. Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa. Front Med (Lausanne) 2023; 10:1208181. [PMID: 37457558 PMCID: PMC10349329 DOI: 10.3389/fmed.2023.1208181] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/15/2023] [Indexed: 07/18/2023] Open
Abstract
The post-viral fatigue syndromes long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have multiple, potentially overlapping, pathological processes. These include persisting reservoirs of virus, e.g., SARS-CoV-2 in long COVID patient's tissues, immune dysregulation with or without reactivation of underlying pathogens, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV6), as we recently described in ME/CFS, and possibly yet unidentified viruses. In the present study we tested saliva samples from two cohorts for IgG against human adenovirus (HAdV): patients with ME/CFS (n = 84) and healthy controls (n = 94), with either mild/asymptomatic SARS-CoV-2 infection or no infection. A significantly elevated anti-HAdV IgG response after SARS-CoV-2 infection was detected exclusively in the patient cohort. Longitudinal/time analysis, before and after COVID-19, in the very same individuals confirmed HAdV IgG elevation after. In plasma there was no HAdV IgG elevation. We conclude that COVID-19 triggered reactivation of dormant HAdV in the oral mucosa of chronic fatigue patients indicating an exhausted dysfunctional antiviral immune response in ME/CFS, allowing reactivation of adenovirus upon stress encounter such as COVID-19. These novel findings should be considered in clinical practice for identification of patients that may benefit from therapy that targets HAdV as well.
Collapse
Affiliation(s)
- Ulf Hannestad
- Department of Biomedicine and Surgery, Division of Cell Biology, Linköping University, Linköping, Sweden
| | - Eirini Apostolou
- Department of Biomedicine and Surgery, Division of Cell Biology, Linköping University, Linköping, Sweden
| | - Per Sjögren
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institute, Stockholm, Sweden
- ME-Center, Bragée Clinics, Stockholm, Sweden
| | - Björn Bragée
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institute, Stockholm, Sweden
- ME-Center, Bragée Clinics, Stockholm, Sweden
| | - Olli Polo
- ME-Center, Bragée Clinics, Stockholm, Sweden
| | - Bo Christer Bertilson
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institute, Stockholm, Sweden
- ME-Center, Bragée Clinics, Stockholm, Sweden
| | - Anders Rosén
- Department of Biomedicine and Surgery, Division of Cell Biology, Linköping University, Linköping, Sweden
| |
Collapse
|
|
27
|
Radke JR, Cook JL. Human adenovirus lung disease: outbreaks, models of immune-response-driven acute lung injury and pandemic potential. Curr Opin Infect Dis 2023; 36:164-170. [PMID: 37093048 PMCID: PMC10133205 DOI: 10.1097/qco.0000000000000919] [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] [Indexed: 04/25/2023]
Abstract
PURPOSE OF REVIEW An overview of epidemic, human adenovirus (HAdV) lung infections with proposed studies of the viral/host immune response interface to better understand mechanisms of immunopathogenesis, for development of improved responses to a potential HAdV pandemic. RECENT FINDINGS Emergent HAdV strains 7, 3, 4, 14 are the most common types associated with infection outbreaks. Recent outbreaks have revealed increased community spread, beyond epidemic group settings. The ongoing circulation of these virulent HAdV strains might allow for further HAdV adaptation, with increased HAdV spread and disease severity in the population that could theoretically result in expansion to a pandemic level. SUMMARY Public health screening has revealed spread of HAdV outbreak strains to the general community. Despite expanded awareness of viral respiratory diseases during the SARS-CoV-2 pandemic, there has been limited, systematic monitoring of HAdV infection in the population. The shift in clinical laboratories to a focus on molecular diagnostics and away from classical methods of viral characterization has reduced the distribution of outbreak HAdV strains to the research community to study mechanisms of pathogenesis. This change risks reduced development of new preventive and therapeutic strategies that could be needed in the event of more widespread HAdV epidemics.
Collapse
Affiliation(s)
- Jay R. Radke
- Boise VA Medical Center and Biomolecular Sciences Graduate Program at Boise State University
| | - James L. Cook
- Division of Infectious Diseases, Department of Medicine, Loyola University Medical Center; Staff Physician and Research Scientist, Infectious Diseases Section, Edward Hines, Jr. VA Hospital
| |
Collapse
|
|
28
|
Lilley CM, Borys E, Picken MM. Adenovirus-Associated Acute Interstitial Nephritis With Graft Survival and Novel Follow-Up Biopsy Findings Including Karyomegaly: A Case Series. Cureus 2023; 15:e38452. [PMID: 37273386 PMCID: PMC10234624 DOI: 10.7759/cureus.38452] [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] [Accepted: 04/30/2023] [Indexed: 06/06/2023] Open
Abstract
Adenoviral infections in post-transplant patients have been described in multiple organ systems, most classically the lung, liver, and alimentary tract. In the genitourinary tract, hemorrhagic cystitis is most frequently observed. Clinically apparent renal involvement with adenovirus is rare, and adenovirus-associated interstitial nephritis (AAIN) is an uncommon cause of renal allograft failure. Here, we present three cases of AAIN in patients who, after prompt diagnosis and treatment adjustment, experienced a return of allograft function. All patients were on standard triple therapy with tacrolimus levels within the target range at the time of biopsy. None of the patients had respiratory symptoms, and despite diarrhea, colon biopsies were negative. Only case one had positive adenovirus serology (IgG only) and case three had positive urine; two patients had leukopenia without neutropenia. Renal biopsies showed a characteristic granulomatous tubulocentric mixed lymphocytic and neutrophilic infiltrate. Adenovirus immunohistochemistry (IHC) showed strong staining in the tubular epithelium (nuclear and cytoplasmic) while staining for polyomavirus was negative. A follow-up biopsy two months after the diagnosis of AAIN in one patient revealed persistent cytopathic effects with negative adenoviral IHC staining while a biopsy at one year in another patient showed glomerular and tubulointerstitial scarring. AAIN is an uncommon but important etiology to consider in cases of acute renal allograft dysfunction. Although the presenting symptoms for AAIN are nonspecific, hematuria is frequently noted. Adenovirus IHC should be considered in cases with granulomatous inflammation associated with necrosis and mixed inflammatory infiltrate. As demonstrated in this single-institution case series, prompt diagnosis can result in the preservation of the renal allograft. Lasting cytopathic effects after adenoviral infection should also be considered in patients with a history, or potential history, of AAIN.
Collapse
Affiliation(s)
- Cullen M Lilley
- Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, USA
| | - Ewa Borys
- Department of Pathology, Loyola University Medical Center, Maywood, USA
| | - Maria M Picken
- Department of Pathology, Loyola University Medical Center, Maywood, USA
| |
Collapse
|