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Kandathil AJ, Thomas DL. The Blood Virome: A new frontier in biomedical science. Biomed Pharmacother 2024; 175:116608. [PMID: 38703502 PMCID: PMC11184943 DOI: 10.1016/j.biopha.2024.116608] [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: 01/08/2024] [Revised: 04/12/2024] [Accepted: 04/17/2024] [Indexed: 05/06/2024] Open
Abstract
Recent advances in metagenomic testing opened a new window into the mammalian blood virome. Comprised of well-known viruses like human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, the virome also includes many other eukaryotic viruses and phages whose medical significance, lifecycle, epidemiology, and impact on human health are less well known and thus regarded as commensals. This review synthesizes available information for the so-called commensal virome members that circulate in the blood of humans considering their restriction to and interaction with the human host, their natural history, and their impact on human health and physiology.
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Affiliation(s)
- Abraham J Kandathil
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David L Thomas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Namuwulya P, Ashraf S, Niebel M, Ssekagiri A, Tushabe P, Kakooza P, Tong L, Bukenya H, Jerome H, Davis C, Birungi M, Turyahabwe I, Mugaga A, Eliku JP, Francis A, Nakabazzi L, Nsubuga F, Katushabe E, Kisakye A, Ampeire I, Nanteza A, Kaleebu P, Bakamutumaho B, Nsamba P, Kazibwe A, da Silva Filipe A, Tweyongyere R, Bwogi J, Thomson EC. Viruses associated with measles-like illnesses in Uganda. J Infect 2024; 88:106148. [PMID: 38588959 PMCID: PMC11060986 DOI: 10.1016/j.jinf.2024.106148] [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: 08/26/2023] [Revised: 03/13/2024] [Accepted: 03/25/2024] [Indexed: 04/10/2024]
Abstract
OBJECTIVES In this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance program in order to inform diagnostic assay selection and vaccination strategies. METHODS We used metagenomic next-generation sequencing (M-NGS) on the Illumina platform to identify viruses associated with MLI (defined as fever and rash in the presence of either cough, coryza or conjunctivitis) in patient samples that had tested IgM negative for measles between 2010 and 2019. RESULTS Viral genomes were identified in 87/271 (32%) of samples, of which 44/271 (16%) contained 12 known viral pathogens. Expected viruses included rubella, human parvovirus B19, Epstein Barr virus, human herpesvirus 6B, human cytomegalovirus, varicella zoster virus and measles virus (detected within the seronegative window-period of infection) and the blood-borne hepatitis B virus. We also detected Saffold virus, human parvovirus type 4, the human adenovirus C2 and vaccine-associated poliovirus type 1. CONCLUSIONS The study highlights the presence of undiagnosed viruses causing MLI in Uganda, including vaccine-preventable illnesses. NGS can be used to monitor common viral infections at a population level, especially in regions where such infections are prevalent, including low and middle income countries to guide vaccination policy and optimize diagnostic assays.
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Affiliation(s)
| | - Shirin Ashraf
- MRC - University of Glasgow Centre for Virus Research (CVR), Glasgow, UK
| | - Marc Niebel
- MRC - University of Glasgow Centre for Virus Research (CVR), Glasgow, UK
| | | | | | | | - Lily Tong
- MRC - University of Glasgow Centre for Virus Research (CVR), Glasgow, UK
| | - Henry Bukenya
- Uganda Virus Research Institute (UVRI), Entebbe, Uganda
| | - Hanna Jerome
- MRC - University of Glasgow Centre for Virus Research (CVR), Glasgow, UK
| | - Chris Davis
- MRC - University of Glasgow Centre for Virus Research (CVR), Glasgow, UK
| | - Molly Birungi
- Uganda Virus Research Institute (UVRI), Entebbe, Uganda
| | | | - Arnold Mugaga
- Uganda Virus Research Institute (UVRI), Entebbe, Uganda
| | | | - Aine Francis
- Uganda Virus Research Institute (UVRI), Entebbe, Uganda
| | | | | | | | | | | | - Ann Nanteza
- College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | | | | | - Peninah Nsamba
- College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | - Anne Kazibwe
- College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | | | - Robert Tweyongyere
- College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda
| | | | - Emma C Thomson
- MRC - University of Glasgow Centre for Virus Research (CVR), Glasgow, UK; London School of Hygiene and Tropical Medicine (LSHTM), London, UK.
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Carmona RDCC, Cilli A, da Costa AC, Reis FC, Leal É, dos Santos FCP, Machado BC, Lopes CS, Afonso AMS, Timenetsky MDCST. Pegivirus Detection in Cerebrospinal Fluid from Patients with Central Nervous System Infections of Unknown Etiology in Brazil by Viral Metagenomics. Microorganisms 2023; 12:19. [PMID: 38257846 PMCID: PMC10818654 DOI: 10.3390/microorganisms12010019] [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: 10/25/2023] [Revised: 11/23/2023] [Accepted: 11/28/2023] [Indexed: 01/24/2024] Open
Abstract
Metagenomic next-generation sequencing (mNGS) methodology serves as an excellent supplement in cases where diagnosis is challenging to establish through conventional laboratory tests, and its usage is increasingly prevalent. Examining the causes of infectious diseases in the central nervous system (CNS) is vital for understanding their spread, managing outbreaks, and effective patient care. In a study conducted in the state of São Paulo, Brazil, cerebrospinal fluid (CSF) samples from 500 patients with CNS diseases of indeterminate etiology, collected between 2017 and 2021, were analyzed. Employing a mNGS approach, we obtained the complete coding sequence of Pegivirus hominis (HPgV) genotype 2 in a sample from a patient with encephalitis (named IAL-425/BRA/SP/2019); no other pathogen was detected. Subsequently, to determine the extent of this virus's presence, both polymerase chain reaction (PCR) and/or real-time PCR assays were utilized on the entire collection. The presence of the virus was identified in 4.0% of the samples analyzed. This research constitutes the first report of HPgV detection in CSF samples in South America. Analysis of the IAL-425 genome (9107 nt) revealed a 90% nucleotide identity with HPgV strains from various countries. Evolutionary analyses suggest that HPgV is both endemic and extensively distributed. The direct involvement of HPgV in CNS infections in these patients remains uncertain.
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Affiliation(s)
| | - Audrey Cilli
- Enteric Disease Laboratory, Virology Center, Adolfo Lutz Institute, Sao Paulo 01246-900, Brazil; (A.C.); (F.C.R.); (B.C.M.)
| | | | - Fabricio Caldeira Reis
- Enteric Disease Laboratory, Virology Center, Adolfo Lutz Institute, Sao Paulo 01246-900, Brazil; (A.C.); (F.C.R.); (B.C.M.)
| | - Élcio Leal
- Institute of Biological Sciences, Federal University of Pará, Belem 66075-000, Brazil;
| | | | - Bráulio Caetano Machado
- Enteric Disease Laboratory, Virology Center, Adolfo Lutz Institute, Sao Paulo 01246-900, Brazil; (A.C.); (F.C.R.); (B.C.M.)
| | - Cristina Santiago Lopes
- Respiratory Disease Laboratory, Virology Center, Adolfo Lutz Institute, Sao Paulo 01246-900, Brazil; (F.C.P.d.S.); (C.S.L.); (A.M.S.A.)
| | - Ana Maria Sardinha Afonso
- Respiratory Disease Laboratory, Virology Center, Adolfo Lutz Institute, Sao Paulo 01246-900, Brazil; (F.C.P.d.S.); (C.S.L.); (A.M.S.A.)
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da Silva AS, de Campos GM, Villanova MG, Bezerra RDS, Santiago LMM, Haddad R, Covas DT, Giovanetti M, Alcantara LCJ, Elias MC, Sampaio SC, Kashima S, Slavov SN. Human Pegivirus-1 Detection and Genotyping in Brazilian Patients with Fulminant Hepatitis. Pathogens 2023; 12:1122. [PMID: 37764930 PMCID: PMC10536510 DOI: 10.3390/pathogens12091122] [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: 04/24/2023] [Revised: 07/20/2023] [Accepted: 08/11/2023] [Indexed: 09/29/2023] Open
Abstract
Fulminant hepatitis is a severe clinical disease characterized by a marked decline in liver function and encephalopathy. In a previous survey, using metagenomics in a group of 27 patients with this clinical condition, we observed an expressive quantity of reads of the Human pegivirus-1 (HPgV-1). Therefore, the objective of this study was to evaluate the frequency, molecular features, and HPgV-1 circulating genotypes in patients with fulminant hepatitis. After testing the collected plasma samples, we discovered twelve samples (44.4%) that were positive for HPgV-1 RNA (using both real-time and nested PCR). The positive samples presented a mean cycle threshold (Ct) of 28.5 (±7.3). Genotyping assignments revealed that all HPgV-1 positive samples belonged to the HPgV-1 genotype 2 (both subgenotypes 2A and 2B were identified). Although HPgV-1 is considered a commensal virus, little is known regarding its prevalence and genotypes in cases of fulminant hepatitis. More research is needed to understand whether HPgV-1 can be implicated in clinical disorders and infectious diseases.
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Affiliation(s)
- Anielly Sarana da Silva
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
| | - Gabriel Montenegro de Campos
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
| | - Marcia Guimarães Villanova
- Department of Gastroenterology, University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14048-900, SP, Brazil;
| | - Rafael dos Santos Bezerra
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
| | - Luciana Maria Mendes Santiago
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
| | - Rodrigo Haddad
- Faculty of Ceilândia, University of Brasília, Brasília 72220-275, DF, Brazil;
| | - Dimas Tadeu Covas
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
| | - Marta Giovanetti
- Instituto Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-009, MG, Brazil;
- Sciences and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, 00128 Rome, Italy;
| | - Luiz Carlos Junior Alcantara
- Sciences and Technologies for Sustainable Development and One Health, Università Campus Bio-Medico di Roma, 00128 Rome, Italy;
| | - Maria Carolina Elias
- Center for Scientific Development, Butantan Institute, São Paulo 05503-900, SP, Brazil; (M.C.E.); (S.C.S.)
| | - Sandra Coccuzzo Sampaio
- Center for Scientific Development, Butantan Institute, São Paulo 05503-900, SP, Brazil; (M.C.E.); (S.C.S.)
| | - Simone Kashima
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
| | - Svetoslav Nanev Slavov
- Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14051-140, SP, Brazil; (A.S.d.S.); (G.M.d.C.); (R.d.S.B.); (L.M.M.S.); (D.T.C.); (S.K.)
- Center for Scientific Development, Butantan Institute, São Paulo 05503-900, SP, Brazil; (M.C.E.); (S.C.S.)
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Zhang F, Chase-Topping M, Guo CG, Woolhouse MEJ. Predictors of human-infective RNA virus discovery in the United States, China, and Africa, an ecological study. eLife 2022; 11:e72123. [PMID: 35666108 PMCID: PMC9278958 DOI: 10.7554/elife.72123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
Background The variation in the pathogen type as well as the spatial heterogeneity of predictors make the generality of any associations with pathogen discovery debatable. Our previous work confirmed that the association of a group of predictors differed across different types of RNA viruses, yet there have been no previous comparisons of the specific predictors for RNA virus discovery in different regions. The aim of the current study was to close the gap by investigating whether predictors of discovery rates within three regions-the United States, China, and Africa-differ from one another and from those at the global level. Methods Based on a comprehensive list of human-infective RNA viruses, we collated published data on first discovery of each species in each region. We used a Poisson boosted regression tree (BRT) model to examine the relationship between virus discovery and 33 predictors representing climate, socio-economics, land use, and biodiversity across each region separately. The discovery probability in three regions in 2010-2019 was mapped using the fitted models and historical predictors. Results The numbers of human-infective virus species discovered in the United States, China, and Africa up to 2019 were 95, 80, and 107 respectively, with China lagging behind the other two regions. In each region, discoveries were clustered in hotspots. BRT modelling suggested that in all three regions RNA virus discovery was better predicted by land use and socio-economic variables than climatic variables and biodiversity, although the relative importance of these predictors varied by region. Map of virus discovery probability in 2010-2019 indicated several new hotspots outside historical high-risk areas. Most new virus species since 2010 in each region (6/6 in the United States, 19/19 in China, 12/19 in Africa) were discovered in high-risk areas as predicted by our model. Conclusions The drivers of spatiotemporal variation in virus discovery rates vary in different regions of the world. Within regions virus discovery is driven mainly by land-use and socio-economic variables; climate and biodiversity variables are consistently less important predictors than at a global scale. Potential new discovery hotspots in 2010-2019 are identified. Results from the study could guide active surveillance for new human-infective viruses in local high-risk areas. Funding FFZ is funded by the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk/). MEJW has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 874735 (VEO) (https://www.veo-europe.eu/).
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Affiliation(s)
- Feifei Zhang
- Usher Institute, University of EdinburghEdinburghUnited Kingdom
| | - Margo Chase-Topping
- Usher Institute, University of EdinburghEdinburghUnited Kingdom
- Roslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghEdinburghUnited Kingdom
| | - Chuan-Guo Guo
- Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong KongHong KongChina
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Stapleton JT. Human Pegivirus Type 1: A Common Human Virus That Is Beneficial in Immune-Mediated Disease? Front Immunol 2022; 13:887760. [PMID: 35707535 PMCID: PMC9190258 DOI: 10.3389/fimmu.2022.887760] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 05/03/2022] [Indexed: 12/25/2022] Open
Abstract
Two groups identified a novel human flavivirus in the mid-1990s. One group named the virus hepatitis G virus (HGV) and the other named it GB Virus type C (GBV-C). Sequence analyses found these two isolates to be the same virus, and subsequent studies found that the virus does not cause hepatitis despite sharing genome organization with hepatitis C virus. Although HGV/GBV-C infection is common and may cause persistent infection in humans, the virus does not appear to directly cause any other known disease state. Thus, the virus was renamed “human pegivirus 1” (HPgV-1) for “persistent G” virus. HPgV-1 is found primarily in lymphocytes and not hepatocytes, and several studies found HPgV-1 infection associated with prolonged survival in people living with HIV. Co-infection of human lymphocytes with HPgV-1 and HIV inhibits HIV replication. Although three viral proteins directly inhibit HIV replication in vitro, the major effects of HPgV-1 leading to reduced HIV-related mortality appear to result from a global reduction in immune activation. HPgV-1 specifically interferes with T cell receptor signaling (TCR) by reducing proximal activation of the lymphocyte specific Src kinase LCK. Although TCR signaling is reduced, T cell activation is not abolished and with sufficient stimulus, T cell functions are enabled. Consequently, HPgV-1 is not associated with immune suppression. The HPgV-1 immunomodulatory effects are associated with beneficial outcomes in other diseases including Ebola virus infection and possibly graft-versus-host-disease following stem cell transplantation. Better understanding of HPgV-1 immune escape and mechanisms of inflammation may identify novel therapies for immune-based diseases.
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Affiliation(s)
- Jack T. Stapleton
- Medicine Service, Iowa City Veterans Administration Healthcare, Iowa City, IA, United States
- Departments of Internal Medicine, Microbiology & Immunology, University of Iowa, Iowa City, IA, United States
- *Correspondence: Jack T. Stapleton,
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Yu Y, Wan Z, Wang JH, Yang X, Zhang C. Review of human pegivirus: Prevalence, transmission, pathogenesis, and clinical implication. Virulence 2022; 13:324-341. [PMID: 35132924 PMCID: PMC8837232 DOI: 10.1080/21505594.2022.2029328] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Human pegivirus (HPgV-1), previously known as GB virus C (GBV-C) or hepatitis G virus (HGV), is a single-stranded positive RNA virus belonging to the genus Pegivirus of the Flaviviridae family. It is transmitted by percutaneous injuries (PIs), contaminated blood and/or blood products, sexual contact, and vertical mother-to-child transmission. It is widely prevalent in general population, especially in high-risk groups. HPgV-1 viremia is typically cleared within the first 1–2 years of infection in most healthy individuals, but may persist for longer periods of time in immunocompromised individuals and/or those co-infected by other viruses. A large body of evidences indicate that HPgV-1 persistent infection has a beneficial clinical effect on many infectious diseases, such as acquired immunodeficiency syndrome (AIDS) and hepatitis C. The beneficial effects seem to be related to a significant reduction of immune activation, and/or the inhabitation of co-infected viruses (e.g. HIV-1). HPgV-1 has a broad cellular tropism for lymphoid and myeloid cells, and preferentially replicates in bone marrow and spleen without cytopathic effect, implying a therapeutic potential. The paper aims to summarize the natural history, prevalence and distribution characteristics, and pathogenesis of HPgV-1, and discuss its association with other human viral diseases, and potential use in therapy as a biovaccine or viral vector.
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Affiliation(s)
- Yaqi Yu
- College of Life Sciences, Henan Normal University, Xinxiang, China.,Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zhenzhou Wan
- Medical Laboratory of Taizhou Fourth People's Hospital, Taizhou, China
| | - Jian-Hua Wang
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Xianguang Yang
- College of Life Sciences, Henan Normal University, Xinxiang, China
| | - Chiyu Zhang
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Fernández-Ruiz M, Forque L, Albert E, Redondo N, Giménez E, López-Medrano F, González E, Polanco N, Ruiz-Merlo T, Parra P, San Juan R, Andrés A, Aguado JM, Navarro D. Human pegivirus type 1 infection in kidney transplant recipients: Replication kinetics and clinical correlates. Transpl Infect Dis 2021; 24:e13771. [PMID: 34921747 DOI: 10.1111/tid.13771] [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: 10/17/2021] [Revised: 11/23/2021] [Accepted: 11/29/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. METHODS We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. RESULTS HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. CONCLUSION Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.
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Affiliation(s)
- Mario Fernández-Ruiz
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Lorena Forque
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Eliseo Albert
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Natalia Redondo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Estela Giménez
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.,Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Esther González
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Natalia Polanco
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Patricia Parra
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.,Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Amado Andrés
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.,Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.,Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - David Navarro
- Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.,Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
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Zimmerman J, Blackard JT. Human pegivirus type 1 infection in Asia-A review of the literature. Rev Med Virol 2021; 32:e2257. [PMID: 34038600 DOI: 10.1002/rmv.2257] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 05/13/2021] [Accepted: 05/17/2021] [Indexed: 12/16/2022]
Abstract
The human pegivirus type 1 (HPgV-1)-as known as hepatitis G virus and GB virus C-is a common single-stranded RNA flavivirus. Because few studies have demonstrated an association between HPgV-1 infection and disease, screening for HPgV-1 is not performed routinely. Nonetheless, a beneficial impact of HPgV-1 infection on HIV disease progression has been reported in multiple studies. Given the burden of HIV in Asia and the complex interactions between viral co-infections and the host, we provide a comprehensive overview of the existing data from Asia on HPgV-1 infection, including the prevalence and circulating genotypes in all Asian countries with data reported. This review highlights the research conducted thus far and emphasizes the need for additional studies on HPgV-1 across the Asian continent.
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Affiliation(s)
- Joseph Zimmerman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Jason T Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Kandathil AJ, Balagopal A. Human Hepegivirus-1: Innocent Traveler, Helpful Symbiote, or Insidious Pathogen? Clin Infect Dis 2021; 71:1229-1231. [PMID: 31671171 DOI: 10.1093/cid/ciz947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 10/08/2019] [Indexed: 12/28/2022] Open
Affiliation(s)
- Abraham J Kandathil
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ashwin Balagopal
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Hoffmann R, Ruegamer T, Schaubächer J, Rohrhofer A, Kirmeß P, Fiebig KM, Schmidt B, Eichler J. Exploring Viral Interference Using Peptides: Molecular Determinants of HIV-1 Inhibition by a Peptide Derived from Human Pegivirus-1 Envelope Protein E2. ChemMedChem 2021; 16:1290-1296. [PMID: 33378104 PMCID: PMC8248410 DOI: 10.1002/cmdc.202000892] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/29/2020] [Indexed: 01/13/2023]
Abstract
Co-infection with the human pegivirus 1 (HPgV-1) often has a beneficial effect on disease progression in HIV-1-infected individuals. Several HPgV-1 proteins and peptides, including a 20-mer peptide (P6-2) derived from the N-terminal region of the HPgV-1 surface protein E2, have been associated with this phenomenon, which is referred to as viral interference. We identified the cysteine residues, the hydrophobic core tetrapeptide, as well as the C-terminal negative charge as key factors for the HIV-1 inhibitory activity of P6-2. Analysis of mutations in P6-2-resistant HIV-1 indicated a binding site for the peptide in the HIV-1 envelope glycoprotein gp120. In fact, P6-2 was shown to bind to soluble gp120, as well as to a peptide presenting the gp120 V3 loop. Furthermore, the HIV-1 inhibitory activity of P6-2 could be revoked by the V3 loop peptide, thus indicating a molecular mechanism that involves interaction of P6-2 with the gp120 V3 loop.
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Affiliation(s)
- Rebecca Hoffmann
- Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany
| | - Tamara Ruegamer
- Institute of Clinical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Johanna Schaubächer
- Institute of Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Anette Rohrhofer
- Institute of Clinical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Peter Kirmeß
- Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany
| | - Karen M Fiebig
- Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany
| | - Barbara Schmidt
- Institute of Clinical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.,Institute of Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Jutta Eichler
- Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany
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Heffron AS, Lauck M, Somsen ED, Townsend EC, Bailey AL, Sosa M, Eickhoff J, Capuano III S, Newman CM, Kuhn JH, Mejia A, Simmons HA, O’Connor DH. Discovery of a Novel Simian Pegivirus in Common Marmosets ( Callithrix jacchus) with Lymphocytic Enterocolitis. Microorganisms 2020; 8:microorganisms8101509. [PMID: 33007921 PMCID: PMC7599636 DOI: 10.3390/microorganisms8101509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/26/2020] [Accepted: 09/28/2020] [Indexed: 11/30/2022] Open
Abstract
From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased enterocolitis-positive marmosets for viruses. In five out of eight common marmosets with lymphocytic enterocolitis, we discovered a novel pegivirus not present in ten matched, clinically normal controls. The novel virus, which we named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide identity) to a strain of simian pegivirus A isolated from a three-striped night monkey (Aotus trivirgatus). We screened 146 living WNPRC common marmosets for SOBV, finding an overall prevalence of 34% (50/146). Over four years, 85 of these 146 animals died or were euthanized. Histological examination revealed 27 SOBV-positive marmosets from this cohort had lymphocytic enterocolitis, compared to 42 SOBV-negative marmosets, indicating no association between SOBV and disease in this cohort (p = 0.0798). We also detected SOBV in two of 33 (6%) clinically normal marmosets screened during transfer from the New England Primate Research Center, suggesting SOBV could be exerting confounding influences on comparisons of common marmoset studies from multiple colonies.
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Affiliation(s)
- Anna S. Heffron
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Michael Lauck
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Elizabeth D. Somsen
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Elizabeth C. Townsend
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Adam L. Bailey
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Megan Sosa
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - Jens Eickhoff
- Department of Biostatistics & Medical Informatics, University of Wisconsin-Madison, Madison, WI 53705, USA;
| | - Saverio Capuano III
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - Christina M. Newman
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
| | - Jens H. Kuhn
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA;
| | - Andres Mejia
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - Heather A. Simmons
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
| | - David H. O’Connor
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53711, USA; (A.S.H.); (M.L.); (E.D.S.); (E.C.T.); (C.M.N.)
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA; (M.S.); (S.C.III); (A.M.); (H.A.S.)
- Correspondence: ; Tel.: +1-608-890-0845
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13
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Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients. Clin Microbiol Rev 2020; 33:33/4/e00027-20. [PMID: 32847820 DOI: 10.1128/cmr.00027-20] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians' radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.
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Fama A, Larson MC, Link BK, Habermann TM, Feldman AL, Call TG, Ansell SM, Liebow M, Xiang J, Maurer MJ, Slager SL, Nowakowski GS, Stapleton JT, Cerhan JR. Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis. Clin Infect Dis 2020; 71:1221-1228. [PMID: 31671178 PMCID: PMC7442854 DOI: 10.1093/cid/ciz940] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 09/20/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Human pegivirus (HPgV) is a single-strand RNA virus belonging to the Flaviviridae. Although no definitive association between HPgV infection and disease has been identified, previous studies have suggested an association of HPgV viremia with risk of lymphomas. METHODS We conducted a systematic review and meta-analysis, including 1 cohort study and 14 case-control studies, assessing the association of HPgV viremia with adult lymphomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model, overall and by geographic region and lymphoma subtype. RESULTS The overall OR for lymphoma was 2.85 (95% CI, 1.98-4.11), with statistically significantly elevated ORs observed in 8 of 15 studies. There was a small amount of heterogeneity among studies (I2 = 28.9%; Q = 18.27, P = .16), and the funnel plot provided no evidence for publication bias. The strongest association with lymphoma risk was observed for studies from Southern Europe (OR, 5.68 [95% CI, 1.98-16.3]), whereas weaker ORs (with 95% CIs) were observed for studies from North America (2.24 [1.76-2.85]), Northern Europe (2.90 [.45-18.7), and the Middle East (2.51 [.87-7.27]), but all of similar magnitude. Participants with HPgV viremia had statistically significantly increased risks (OR [95% CI]) for developing diffuse large B-cell (3.29 [1.63-6.62]), follicular (3.01 [1.95-4.63]), marginal zone (1.90 [1.13-3.18]), and T-cell (2.11 [1.17-3.89]) lymphomas, while the risk for Hodgkin lymphoma (3.53 [.48-25.9]) and chronic lymphocytic leukemia (1.45 [.45-4.66]) were increased but did not achieve statistical significance. CONCLUSIONS This meta-analysis supports a positive association of HPgV viremia with lymphoma risk, overall and for the major lymphoma subtypes.
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Affiliation(s)
- Angelo Fama
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Ematologia, Azienda Unità Sanitaria Locale, Istituto di Ricovero e Cura a Carattere Scientificodi Reggio Emilia, Reggio Emilia, Italy
| | - Melissa C Larson
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Brian K Link
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Thomas M Habermann
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Andrew L Feldman
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Timothy G Call
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Stephen M Ansell
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Mark Liebow
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jinhua Xiang
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
- Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA
| | - Matthew J Maurer
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Susan L Slager
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Grzegorz S Nowakowski
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jack T Stapleton
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
- Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA
| | - James R Cerhan
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
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15
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Porter AF, Pettersson JHO, Chang WS, Harvey E, Rose K, Shi M, Eden JS, Buchmann J, Moritz C, Holmes EC. Novel hepaci- and pegi-like viruses in native Australian wildlife and non-human primates. Virus Evol 2020; 6:veaa064. [PMID: 33240526 PMCID: PMC7673076 DOI: 10.1093/ve/veaa064] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The Flaviviridae family of positive-sense RNA viruses contains important pathogens of humans and other animals, including Zika virus, dengue virus, and hepatitis C virus. The Flaviviridae are currently divided into four genera-Hepacivirus, Pegivirus, Pestivirus, and Flavivirus-each with a diverse host range. Members of the genus Hepacivirus are associated with an array of animal species, including humans, non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa, also including humans. Using a combination of total RNA and whole-genome sequencing we identified four novel hepaci-like viruses and one novel variant of a known hepacivirus in five species of Australian wildlife. The hosts infected comprised native Australian marsupials and birds, as well as a native gecko (Gehyra lauta). From these data we identified a distinct marsupial clade of hepaci-like viruses that also included an engorged Ixodes holocyclus tick collected while feeding on Australian long-nosed bandicoots (Perameles nasuta). Distinct lineages of hepaci-like viruses associated with geckos and birds were also identified. By mining the SRA database we similarly identified three new hepaci-like viruses from avian and primate hosts, as well as two novel pegi-like viruses associated with primates. The phylogenetic history of the hepaci- and pegi-like viruses as a whole, combined with co-phylogenetic analysis, provided support for virus-host co-divergence over the course of vertebrate evolution, although with frequent cross-species virus transmission. Overall, our work highlights the diversity of the Hepacivirus and Pegivirus genera as well as the uncertain phylogenetic distinction between.
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Affiliation(s)
- Ashleigh F Porter
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
| | - John H-O Pettersson
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
| | - Wei-Shan Chang
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
| | - Erin Harvey
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
| | - Karrie Rose
- Australian Registry of Wildlife Health, Taronga Conservation Society Australia, Mosman 2088, Australia
| | - Mang Shi
- School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - John-Sebastian Eden
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
| | - Jan Buchmann
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
| | - Craig Moritz
- Research School of Biology, Centre for Biodiversity Analysis, Australian National University, Acton, ACT, Australia
| | - Edward C Holmes
- School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia
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16
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Tomlinson JE, Wolfisberg R, Fahnøe U, Sharma H, Renshaw RW, Nielsen L, Nishiuchi E, Holm C, Dubovi E, Rosenberg BR, Tennant BC, Bukh J, Kapoor A, Divers TJ, Rice CM, Van de Walle GR, Scheel TKH. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. PLoS Pathog 2020; 16:e1008677. [PMID: 32649726 PMCID: PMC7375656 DOI: 10.1371/journal.ppat.1008677] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 07/22/2020] [Accepted: 06/02/2020] [Indexed: 12/20/2022] Open
Abstract
Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1–4% of healthy individuals and another 5–13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler’s disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler’s disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3’ terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2–3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2. Transmissible hepatitis in horses (Theiler’s disease) has been known for 100 years without knowledge of causative infectious agents. Recently, two novel equine pegiviruses (EPgV) were discovered. Whereas EPgV-1 was not associated to disease, the other was identified in an outbreak of acute serum hepatitis and therefore named Theiler’s disease-associated virus (TDAV). This finding was surprising since human and monkey pegiviruses typically cause long-term infection without associated clinical disease. Whereas no subsequent reports link TDAV to disease, the original association to hepatitis has not been formally examined. Here, we studied EPgV-1 and TDAV and found that their natural history of infection in horses were remarkably similar. Examination of various tissues identified the bone marrow as the primary site of replication for both viruses with no evidence of replication in the liver. To exclude potential effects of other infectious agents, we developed molecular full-length clones for EPgV-1 and TDAV and were able to initiate infection in horses using derived synthetic viral genetic material. This demonstrated long-term infection, but no association with hepatitis. These findings call into question the connection between TDAV, liver infection, and hepatitis in horses.
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Affiliation(s)
- Joy E. Tomlinson
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Raphael Wolfisberg
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Ulrik Fahnøe
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Himanshu Sharma
- Center for Vaccines and Immunity, Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States of America
| | - Randall W. Renshaw
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Louise Nielsen
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Eiko Nishiuchi
- Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America
| | - Christina Holm
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Edward Dubovi
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Brad R. Rosenberg
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Bud C. Tennant
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Jens Bukh
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Amit Kapoor
- Center for Vaccines and Immunity, Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States of America
| | - Thomas J. Divers
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Charles M. Rice
- Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America
| | - Gerlinde R. Van de Walle
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America
| | - Troels K. H. Scheel
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
- Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America
- * E-mail:
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Arhab Y, Bulakhov AG, Pestova TV, Hellen CU. Dissemination of Internal Ribosomal Entry Sites (IRES) Between Viruses by Horizontal Gene Transfer. Viruses 2020; 12:E612. [PMID: 32512856 PMCID: PMC7354566 DOI: 10.3390/v12060612] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/01/2020] [Accepted: 06/02/2020] [Indexed: 12/19/2022] Open
Abstract
Members of Picornaviridae and of the Hepacivirus, Pegivirus and Pestivirus genera of Flaviviridae all contain an internal ribosomal entry site (IRES) in the 5'-untranslated region (5'UTR) of their genomes. Each class of IRES has a conserved structure and promotes 5'-end-independent initiation of translation by a different mechanism. Picornavirus 5'UTRs, including the IRES, evolve independently of other parts of the genome and can move between genomes, most commonly by intratypic recombination. We review accumulating evidence that IRESs are genetic entities that can also move between members of different genera and even between families. Type IV IRESs, first identified in the Hepacivirus genus, have subsequently been identified in over 25 genera of Picornaviridae, juxtaposed against diverse coding sequences. In several genera, members have either type IV IRES or an IRES of type I, II or III. Similarly, in the genus Pegivirus, members contain either a type IV IRES or an unrelated type; both classes of IRES also occur in members of the genus Hepacivirus. IRESs utilize different mechanisms, have different factor requirements and contain determinants of viral growth, pathogenesis and cell type specificity. Their dissemination between viruses by horizontal gene transfer has unexpectedly emerged as an important facet of viral evolution.
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Affiliation(s)
| | | | | | - Christopher U.T. Hellen
- Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA; (Y.A.); (A.G.B.); (T.V.P.)
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18
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Fabrizi F, Vecchi De AF, Lunghi G, Finazzi S, Bisegna S, Ponticelli C. Epidemiology of GB Virus C/Hepatitis G Virus Infection in Patients on Peritoneal Dialysis. Perit Dial Int 2020. [DOI: 10.1177/089686080202200317] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background A new genus in the family Flaviviridae has recently been discovered; it has provisionally been designated GBV-C/HGV. As determined by virologic techniques [reverse-transcription polymerase chain reaction (RT-PCR)], infection with GBV-C/HGV is frequent in renal transplant (RT) recipients and in patients on chronic hemodialysis (HD). The epidemiology of GBV-C/HGV infection in patients on peritoneal dialysis is scarce and mostly based on RT-PCR technology. Purpose We report on the prevalence (as detected by serologic and virologic techniques) and the risk factors for GBV-C/HGV infection in a cohort of patients on continuous ambulatory peritoneal dialysis (CAPD). We also tested a control group of blood donors. Methods Infection by GBV-C/HGV was assessed by serologic and virologic techniques. Cases of GBV-C/HGV viremia (GBV-C/HGV RNA) were detected by RT-PCR. Antibodies to the envelope protein of GBV-C/HGV (anti-E2 GBV-C/HGV antibody) were analyzed by serologic methods. Results We found a high frequency [17/85 (20%)] of GBV-C/HGV. The rates of GBV-C/HGV viremia and anti-E2 GBV-C/HGV positivity were 10.5% (9/85) and 10.5% (9/85) respectively. In most patients [17/18 (94%)], the presence of anti-E2 GBV-C/HGV antibody was associated with clearance of GBV-C/HGV from serum. No relationship was noted between anti-E2 GBV-C/HGV antibody (or GBV-C/HGV viremia) and age, sex, race, time on dialysis, anti-HCV antibody, HBsAg status, and anti-HIV positivity. The frequency of GBV-C/HGV infection in CAPD patients was much higher than that in blood donors, even if the difference did not approach statistical significance. No associations between GBV-C/HGV positivity and biochemical liver tests [aminotransferase and gamma glutamyl transpeptidase (GGT)] were apparent. Conclusions Infection by GBV-C/HGV as detected by RT-PCR and anti-E2 antibody was common in patients on CAPD and in controls alike. No association was seen between GBV-C/HGV and various demographic or clinical factors. The clinical significance of GBV-C/HGV in CAPD remains unclear. Larger investigations are in progress.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephology and Dialysis General Hospital, Melegnano, Italy
| | | | - Giovanna Lunghi
- Institute of Hygiene and Preventive Medicine, General Hospital, Melegnano, Italy
| | - Silvia Finazzi
- Division of Nephology and Dialysis General Hospital, Melegnano, Italy
| | - Sergio Bisegna
- Maggiore Hospital, Policlinico IRCCS, Milan, and Nephrology Unit, General Hospital, Melegnano, Italy
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Henry R. Etymologia: Pegivirus. Emerg Infect Dis 2020. [PMCID: PMC6986853 DOI: 10.3201/eid2602.et2602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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20
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Yang N, Dai R, Zhang X. Global prevalence of human pegivirus-1 in healthy volunteer blood donors: a systematic review and meta-analysis. Vox Sang 2019; 115:107-119. [PMID: 31845353 DOI: 10.1111/vox.12876] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/22/2019] [Accepted: 11/26/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES The local prevalence of HPgV-1 has been reported from different countries worldwide, but the global prevalence of HPgV-1 remains unknown. The aim of this systematic review and meta-analysis was to gather data from the literature to estimate the prevalence of HPgV-1 in healthy volunteer blood donors in the world. MATERIALS AND METHODS We searched PubMed, EMBASE, Scopus and Google Scholar databases for records up to January 2019 and included studies reporting HPgV-1 virus prevalence amongst healthy volunteer blood donors based on the detection of HPgV-1 RNA. RESULTS In all, we included 79 studies for the systematic review and 63 for the meta-analysis. Based on the random effect meta-analysis of 35 468 volunteer blood donors, we found the global prevalence of HPgV-1 to be 3·1% (95% CI, 2·4-4·1). The pooled prevalences of HPgV-1 were 1·7% (95% CI, 1·1-2·6) in North America, 9·1% (95% CI, 6·4-12·7) in South America, 2·3% (95% CI, 2%, 2·8) in Europe and 2·4% (95% CI, 1·4-4) in Asia. Subgroup analyses based on age, gender or risk factors were not possible. CONCLUSION Approximately 3 in 100 blood donations worldwide are positive for HPgV-1 increasing the risk of infection from transfusion of their components to subsequent recipients. Further research on virus pathogenicity is required before recommending routine screening of HPgV-1 for healthy volunteer blood donors.
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Affiliation(s)
- Na Yang
- Yantai Central Blood Station, Yantai, China
| | - Run Dai
- Yantai Central Blood Station, Yantai, China
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21
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Mrzljak A, Tabain I, Premac H, Bogdanic M, Barbic L, Savic V, Stevanovic V, Jelic A, Mikulic D, Vilibic-Cavlek T. The Role of Emerging and Neglected Viruses in the Etiology of Hepatitis. Curr Infect Dis Rep 2019; 21:51. [PMID: 31754812 DOI: 10.1007/s11908-019-0709-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW In this review, we present the overview of emerging and neglected viruses associated with liver involvement. RECENT FINDINGS Hepatitis E virus (HEV) emerged in the last two decades, causing hepatitis in many parts of the world. Moreover, liver involvement was also described in some emerging arboviral infections. Many reports showed dengue-associated liver injury; however, chikungunya, West Nile, tick-borne encephalitis, and Zika virus are rarely associated with clinically manifest liver disease. In addition, some neglected highly prevalent viruses such as adenoviruses and parvovirus B19 are capable of causing hepatitis in specific population groups. Anelloviruses (torque teno virus/torque teno mini virus/torque teno midi virus, SEN virus), human bocavirus, pegiviruses, and lymphocytic choriomeningitis virus have shown a little potential for causing hepatitis, but their role in the etiology of liver disease remains to be determined. In addition to the well-known hepatotropic viruses, many emerging and neglected viruses have been associated with liver diseases. The number of emerging zoonotic viruses has been increasingly recognized. While zoonotic potential of HEV is well documented, the recent identification of new hepatitis-related animal viruses such as HEV strains from rabbits and camels, non-primate hepaciviruses in domestic dogs and horses, as well as equine and porcine pegivirus highlights the possible zoonotic transmission in the context of "One Health." However, zoonotic potential and hepatotropism of animal hepatitis viruses remain to be determined.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Salata 3b, 10000, Zagreb, Croatia.
- School of Medicine, University of Zagreb, Zagreb, Croatia.
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Hrvoje Premac
- Department of Medicine, Varazdin General Hospital, Varazdin, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Vladimir Savic
- Poultry Center, Laboratory for Virology and Serology, Croatian Veterinary Institute, Zagreb, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Ana Jelic
- Department of Medicine, Merkur University Hospital, Salata 3b, 10000, Zagreb, Croatia
| | - Danko Mikulic
- Department of Surgery, Merkur University Hospital, Zagreb, Croatia
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
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22
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Wang H, Wan Z, Xu R, Guan Y, Zhu N, Li J, Xie Z, Lu A, Zhang F, Fu Y, Tang S. A Novel Human Pegivirus, HPgV-2 (HHpgV-1), Is Tightly Associated With Hepatitis C Virus (HCV) Infection and HCV/Human Immunodeficiency Virus Type 1 Coinfection. Clin Infect Dis 2019; 66:29-35. [PMID: 29020289 DOI: 10.1093/cid/cix748] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 08/17/2017] [Indexed: 12/28/2022] Open
Abstract
Background Human pegivirus type 2 (HPgV-2) is a novel blood-borne human pegivirus that mainly infects hepatitis C virus (HCV)-infected subjects. We have investigated the prevalence of HPgV-2 in China, its association with HCV and human immunodeficiency virus type 1 (HIV-1), and the impact on HCV viral load and liver damage. Methods A cross-sectional study was conducted with both blood donors and HCV- and HIV-1-infected patients in Guangzhou, China. All subjects were screened for anti-HPgV-2 and HPgV-2 RNA. Demographic and clinical information were obtained from electronic medical records. Results We tested 8198 serum or plasma samples. Only 0.15% (6/4017) of healthy blood donors were positive for anti-HPgV-2 and negative for HPgV-2 RNA. No HPgV-2 viremia was detected in hepatitis B virus- or HIV-1-monoinfected individuals. The relatively high frequency of HPgV-2 infection was observed in 1.23% (30/2440) and 0.29% (7/2440) of HCV-infected persons by serological assay and reverse-transcription polymerase chain reaction, respectively. Furthermore, anti-HPgV-2 and HPgV-2 RNA were detected in 8.91% (18/202) and 3.47% (7/202), respectively, of HCV/HIV-1-coinfected subjects. HPgV-2 persistent infection was documented in about 30% of anti-HPgV-2-positive individuals. In addition, HPgV-2 infection may not affect HCV-related liver injury and HCV viral load. Conclusions Our results indicate the rarity of HPgV-2 infection in the general population and tight association with HCV, in particular with HCV/HIV-1 coinfection. HPgV-2 appears not to worsen HCV-related liver damage. Our study provides new findings about the association of HPgV-2 and HCV/HIV-1 and the impact of HPgV-2 infection on HCV replication and pathogenesis.
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Affiliation(s)
- Haiying Wang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Epidemiology, School of Public Health, Southern Medical University
| | - Zhengwei Wan
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Epidemiology, School of Public Health, Southern Medical University
| | - Ru Xu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Yujuan Guan
- Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Naling Zhu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Epidemiology, School of Public Health, Southern Medical University
| | - Jianping Li
- Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhiwei Xie
- Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Aiqi Lu
- Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Fuchun Zhang
- Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yongshui Fu
- Guangzhou Blood Center, Guangzhou, Guangdong, China
| | - Shixing Tang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Epidemiology, School of Public Health, Southern Medical University
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Izumi T, Sakata K, Okuzaki D, Inokuchi S, Tamura T, Motooka D, Nakamura S, Ono C, Shimokawa M, Matsuura Y, Mori M, Fukuhara T, Yoshizumi T. Characterization of human pegivirus infection in liver transplantation recipients. J Med Virol 2019; 91:2093-2100. [PMID: 31350911 DOI: 10.1002/jmv.25555] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 07/24/2019] [Indexed: 12/23/2022]
Abstract
Approximately 2% of healthy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood-borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. Here, we examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and patients with hepatectomy and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 patients with hepatectomy who received care at the Kyusyu University Hospital between May 1997 and September 2017. Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and 2 patients (1.1%) had HPgV viremia, respectively. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion because HPgV RNA was detected from the blood bag transfused to the recipient during LT. We reviewed the available literature on the prevalence HPgV infections in other organ-transplanted patients and whether they impacted clinical outcomes. They also had the higher prevalence of HPgV infection, while it appears to be of low or no consequences. In addition, HPgV infection induced the upregulation of interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells. LT recipients had higher HPgV viremia compared to patients with hepatectomy. Although HPgV infection was not associated with LT-related outcomes, it induced ISG expression in recipients.
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Affiliation(s)
- Takuma Izumi
- Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.,Department of Surgery and Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Kazuhito Sakata
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Daisuke Okuzaki
- Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Shoichi Inokuchi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Tomokazu Tamura
- Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Daisuke Motooka
- Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Shota Nakamura
- Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Chikako Ono
- Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Masahiro Shimokawa
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Yoshiharu Matsuura
- Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Takasuke Fukuhara
- Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
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24
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Slavov SN, Maraninchi Silveira R, Hespanhol MR, Sauvage V, Rodrigues ES, Fontanari Krause L, Bittencourt HT, Caro V, Laperche S, Covas DT, Kashima S. Human pegivirus-1 (HPgV-1) RNA prevalence and genotypes in volunteer blood donors from the Brazilian Amazon. Transfus Clin Biol 2019; 26:234-239. [PMID: 31277987 DOI: 10.1016/j.tracli.2019.06.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 06/09/2019] [Indexed: 12/20/2022]
Abstract
OBJECTIVES The objectives of this study were to evaluate the prevalence of Human Pegivirus-1 (HPgV-1) viremia and genotype diversity among healthy blood donors from the Eastern Brazilian Amazon (city of Macapá, State of Amapá). There is little information for prevalence and circulation of HPgV-1 in this remote Brazilian region. MATERIALS AND METHODS We conducted a study evaluating the HPgV-1 RNA prevalence and circulating genotypes in 431 volunteer blood donors originating from the Eastern Brazilian Amazon. The obtained HPgV-1 positive samples were submitted to sequencing and genotyping analysis in order to examine the genotype diversity of this virus in the Brazilian Amazon. RESULTS Our results demonstrated a prevalence of HPgV-1 RNA in 9.5% of the tested blood donors. The phylogenetic analyses of the detected positive samples showed the presence of HPgV-1 genotypes 1, 2 and 3. The most frequently detected genotype was 2 (78.0% of the cases) represented by sub-genotypes 2A (39.0%) and 2B (39.0%). At lower rates, genotypes 1 (14.6%) and 3 (7.4%) were also detected. CONCLUSION Our results revealed the presence of genotypes with European, Asiatic and African endemicity in Amazonian blood donors, probably due to the complex miscegenation processes that took place in this Brazilian region. More investigations, including information for the prevalence of HPgV-1 RNA in blood donors from other Latin American countries are needed to estimate the viremic rates and genotype distribution of this virus in a highly diverse continent like South America.
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Affiliation(s)
- S N Slavov
- Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil; Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil.
| | - R Maraninchi Silveira
- Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil
| | - M R Hespanhol
- Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil
| | - V Sauvage
- Institut national de la transfusion Sanguine (INTS), département d'études des Agents transmissibles par le sang (DATS), Centre national de référence risques infectieux transfusionnels, 75015 Paris, France
| | - E S Rodrigues
- Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil
| | - L Fontanari Krause
- Laboratory of Biosciences, Franciscan University, 97010-030 Santa Maria, Rio Grande do Sul, Brazil
| | - H T Bittencourt
- Institute of Hematology and Hemotherapy of Amapá, 68900-074 Macapá, Amapá, Brazil
| | - V Caro
- Pole for Genotyping of Pathogens (PGP), Laboratory for Urgent Response to Biological Threats, Environment and Infectious Risks Research and Expertise Unit, Institut Pasteur, 75724 Paris, France
| | - S Laperche
- Institut national de la transfusion Sanguine (INTS), département d'études des Agents transmissibles par le sang (DATS), Centre national de référence risques infectieux transfusionnels, 75015 Paris, France
| | - D T Covas
- Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil
| | - S Kashima
- Regional Blood Center of Ribeirão Preto, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14051-140 Ribeirão Preto, São Paulo, Brazil
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25
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Wang T, Chen J, Zhang Q, Huang X, Xie N, Zhang J, Cai T, Zhang Y, Xiong H. Prevalence of hepatitis G virus infection among 67,348 blood donors in mainland China. BMC Public Health 2019; 19:685. [PMID: 31159757 PMCID: PMC6547458 DOI: 10.1186/s12889-019-6948-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/07/2019] [Indexed: 01/11/2023] Open
Abstract
Background Hepatitis G virus (HGV) infection transmitted from blood donors is a concern in China, as many articles about HGV infection in Chinese blood donors from different provinces have been published. This study aimed to evaluate the overall prevalence of HGV infection in Chinese blood donors and analyse the potential risk of HGV infection through blood transfusion in China. Methods We performed a literature search in PubMed, EMBASE, Web of Science, the Chinese BioMedical Literature Database (CBM) and the China National Knowledge Infrastructure (CNKI) up to October 2018 regarding the prevalence of HGV in Chinese blood donors. Eligibility assessment and data extraction were conducted independently by 2 researchers, and meta-analysis was performed to synthesize the data. Heterogeneity was evaluated using Cochran’s Q test and quantified using the I2 statistic. Subgroup analyses were performed to identify the possible sources of heterogeneity. Publication bias was assessed using both funnel plot and Egger’s tests. Results A total of 102 studies with 67,348 blood donors published from 1996 to 2016 and covering 26 provinces or municipalities were included for further analyses. The pooled prevalence of HGV was 3.91% (95%CI: 3.18–4.71%) by enzyme immune assay/enzyme linked immunosorbent assay (EIA/ELISA) and 3.25% (95%CI: 2.35–4.26%) by polymerase chain reaction (PCR). The prevalence of HGV may be significantly affected by region, province or municipality and potentially by the paid/voluntary status of the blood donors. No significant difference was found between plasma and full blood donation. Conclusions The prevalence of HGV in blood donors from China was similar to that in blood donors from many other countries and higher than that of some other hepatitis viruses, such as hepatitis B virus. The risk of transfusion-transmitted HGV still exists after routine blood donor screening, especially in those patients coinfected with other hepatitis viruses and/or HIV. On the basis of our study, we may suggest adding HGV screening for blood transfusions in mainland China in the future. Electronic supplementary material The online version of this article (10.1186/s12889-019-6948-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Taiwu Wang
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, People's Republic of China.,Center for Disease Control and Prevention of Eastern Theater Command, Nanjing, 210002, People's Republic of China
| | - Juecai Chen
- The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, People's Republic of China
| | - Qi Zhang
- Center for Disease Control and Prevention of Eastern Theater Command, Nanjing, 210002, People's Republic of China
| | - Xia Huang
- Chongqing Blood Center, Chongqing, 400015, People's Republic of China
| | - Nanzhen Xie
- Chongqing General Hospital, Chongqing, 400013, People's Republic of China
| | - Jinhai Zhang
- Center for Disease Control and Prevention of Eastern Theater Command, Nanjing, 210002, People's Republic of China
| | - Tongjian Cai
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, People's Republic of China
| | - Yao Zhang
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, People's Republic of China.
| | - Hongyan Xiong
- Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, People's Republic of China.
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Bukowska-Ośko I, Perlejewski K, Pawełczyk A, Rydzanicz M, Pollak A, Popiel M, Cortés KC, Paciorek M, Horban A, Dzieciątkowski T, Radkowski M, Laskus T. Human Pegivirus in Patients with Encephalitis of Unclear Etiology, Poland. Emerg Infect Dis 2019; 24:1785-1794. [PMID: 30226156 PMCID: PMC6154136 DOI: 10.3201/eid2410.180161] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Sequence analysis of human pegivirus from 3 patients indicates that the central nervous system constitutes a separate viral compartment from serum. Human pegivirus (HPgV), previously called hepatitis G virus or GB virus C, is a lymphotropic virus with undefined pathology. Because many viruses from the family Flaviviridae, to which HPgV belongs, are neurotropic, we studied whether HPgV could infect the central nervous system. We tested serum and cerebrospinal fluid samples from 96 patients with a diagnosis of encephalitis for a variety of pathogens by molecular methods and serology; we also tested for autoantibodies against neuronal antigens. We found HPgV in serum and cerebrospinal fluid from 3 patients who had encephalitis of unclear origin; that is, all the markers that had been tested were negative. Single-strand confirmation polymorphism and next-generation sequencing analysis revealed differences between the serum and cerebrospinal fluid–derived viral sequences, which is compatible with the presence of a separate HPgV compartment in the central nervous system. It is unclear whether HPgV was directly responsible for encephalitis in these patients.
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27
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Wang H, Wan Z, Sun Q, Zhu N, Li T, Ren X, An X, Deng S, Wu Y, Li X, Li L, Li J, Tong Y, Tang S. Second Human Pegivirus in Hepatitis C Virus-Infected and Hepatitis C Virus/HIV-1-Co-infected Persons Who Inject Drugs, China. Emerg Infect Dis 2019; 24:908-911. [PMID: 29664364 PMCID: PMC5938795 DOI: 10.3201/eid2405.161162] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
We report the presence of the second human pegivirus (HPgV-2) in Guangdong and Sichuan Provinces in China. The prevalence of HPgV-2 in hepatitis C virus/HIV-1–co-infected persons who inject drugs was 12.9% in Guangdong and 15.9% in Sichuan. This population is at high risk for HPgV-2 infection.
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28
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Rodrigues TCS, Subramaniam K, McCulloch SD, Goldstein JD, Schaefer AM, Fair PA, Reif JS, Bossart GD, Waltzek TB. Genomic characterization of a novel pegivirus species from free-ranging bottlenose dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida. Virus Res 2019; 263:98-101. [PMID: 30633958 DOI: 10.1016/j.virusres.2019.01.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/07/2019] [Accepted: 01/08/2019] [Indexed: 11/15/2022]
Abstract
We report the discovery of the first cetacean pegivirus (family Flaviviridae) using a next-generation sequencing approach. One of two infected bottlenose dolphins had elevated activities of liver enzymes, which may suggest hepatocellular injury. Further research is needed to determine the epidemiology and pathogenicity of dolphin pegivirus.
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Affiliation(s)
| | | | - Stephen D McCulloch
- Protect Wild Dolphins Alliance, 2046 Treasure Coast Plaza, 32960, Vero Beach, FL, USA
| | - Juli D Goldstein
- Protect Wild Dolphins Alliance, 2046 Treasure Coast Plaza, 32960, Vero Beach, FL, USA
| | - Adam M Schaefer
- Florida Atlantic University, 5600 US 1, North, 34946, Fort Pierce, FL, USA
| | - Patricia A Fair
- Medical University of South Carolina, 179 Ashley Ave, 29425, Charleston, SC, USA
| | - John S Reif
- Colorado State University, 102 Administration Bldg, 80523, Fort Collins, CO, USA
| | - Gregory D Bossart
- Georgia Aquarium, 225 Baker Street, 30313, Atlanta, GA, USA; University of Miami, PO Box 016960 (R-46), 33101, Miami, FL, USA
| | - Thomas B Waltzek
- University of Florida, 2187 Mowry Road, 32611, Gainesville, FL, USA.
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29
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Jordier F, Deligny ML, Barré R, Robert C, Galicher V, Uch R, Fournier PE, Raoult D, Biagini P. Human pegivirus isolates characterized by deep sequencing from hepatitis C virus-RNA and human immunodeficiency virus-RNA-positive blood donations, France. J Med Virol 2018; 91:38-44. [PMID: 30133782 DOI: 10.1002/jmv.25290] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/14/2018] [Indexed: 01/18/2023]
Abstract
Human pegivirus (HPgV, formerly GBV-C) is a member of the genus Pegivirus, family Flaviviridae. Despite its identification more than 20 years ago, both natural history and distribution of this viral group in human hosts remain under exploration. Analysis of HPgV genomes characterized up to now points out the scarcity of French pegivirus sequences in databases. To bring new data regarding HPgV genomic diversity, we investigated 16 French isolates obtained from hepatitis C virus-RNA and human immunodeficiency virus-RNA-positive blood donations following deep sequencing and coupled molecular protocols. Initial phylogenetic analysis of 5'-untranslated region (5'-UTR)/E2 partial sequences permitted to assign HPgV isolates to genotypes 2 (n = 15) and 1 (n = 1), with up to 16% genetic diversity observed for both regions considered. Seven nearly full-length representative genomes were characterized subsequently, with complete polyprotein coding sequences exhibiting up to 13% genetic diversity; closest nucleotide (nt) divergence with available HPgV sequences was in the range 7% to 11%. A 36 nts deletion located on the NS4B coding region (N-terminal part, 12 amino acids) of the genotype 1 HPgV genome characterized was identified, along with single nucleotide deletions in two genotype 2, 5'-UTR sequences.
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Affiliation(s)
- François Jordier
- Biologie des Groupes Sanguins, Etablissement Français du Sang Provence Alpes Côte d'Azur Corse, Aix Marseille University, CNRS, EFS, ADES, Marseille, France
| | - Marie-Laurence Deligny
- Biologie des Groupes Sanguins, Etablissement Français du Sang Provence Alpes Côte d'Azur Corse, Aix Marseille University, CNRS, EFS, ADES, Marseille, France
| | - Romain Barré
- Biologie des Groupes Sanguins, Etablissement Français du Sang Provence Alpes Côte d'Azur Corse, Aix Marseille University, CNRS, EFS, ADES, Marseille, France
| | - Catherine Robert
- UMR MEPHI, IRD, Aix Marseille University, AP-HM, IHU Méditerranée-Infection, Marseille, France
| | - Vital Galicher
- Biologie des Groupes Sanguins, Etablissement Français du Sang Provence Alpes Côte d'Azur Corse, Aix Marseille University, CNRS, EFS, ADES, Marseille, France
| | - Rathviro Uch
- Biologie des Groupes Sanguins, Etablissement Français du Sang Provence Alpes Côte d'Azur Corse, Aix Marseille University, CNRS, EFS, ADES, Marseille, France
| | - Pierre-Edouard Fournier
- UMR VITROME, IRD, Aix Marseille University, SSA, AP-HM, IHU Méditerranée-Infection, Marseille, France
| | - Didier Raoult
- UMR MEPHI, IRD, Aix Marseille University, AP-HM, IHU Méditerranée-Infection, Marseille, France
| | - Philippe Biagini
- Biologie des Groupes Sanguins, Etablissement Français du Sang Provence Alpes Côte d'Azur Corse, Aix Marseille University, CNRS, EFS, ADES, Marseille, France
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Inhibition of HIV-1 infection by human pegivirus type 1-derived peptides is affected by human pegivirus type 1 genotype and HIV-1 coreceptor tropism. AIDS 2018; 32:1951-1957. [PMID: 29912064 DOI: 10.1097/qad.0000000000001926] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE(S) Up to 40% of HIV-1 infected individuals are coinfected with human pegivirus type 1 (HPgV-1). The majority of studies, but not all, have reported a beneficial effect of HPgV-1 coinfection on HIV-1 disease progression. So far, the impact of different HPgV-1 genotypes on different HIV-1 subtypes remains unclear. METHODS Peptides derived from HPgV-1 envelope protein E2, and representing different viral genotypes, were synthesized using Fmoc/t-Bu-based solid phase peptide synthesis. The inhibitory effect of these peptides on the infection of reporter cell lines was tested using an HIV-1 subtype panel representing clades A (n = 2), AG (n = 2), B (n = 6), C (n = 2), D (n = 2), F (n = 2), G (n = 1), G/H (n = 1), and group O (n = 2). RESULTS HIV-1 infection was blocked more efficiently by peptides derived from HPgV-1 GT2 than GT1 (P = 0.05). The HIV-1 subtype did not affect the degree of inhibition by a peptide derived from HPgV-1 GT2. All CXCR4-/dual-tropic isolates (n = 12), but only half (four out of eight) CCR5-tropic viruses were inhibited by this peptide (P = 0.014). CONCLUSION Our data indicate that the inhibitory effect of peptides derived from HPgV-1 E2 protein is dependent on the genotype, suggesting that coinfection with HPgV-1 GT1 is less likely to confer a beneficial effect on HIV-1 disease progression than GT2. The preferential suppression of more pathogenic CXCR4-tropic HIV-1 by peptides derived from HPgV-1 GT2 may explain the favorable effect in patients harboring these HIV-1 isolates. Consequently, HPgV-1 genotype and HIV-1 coreceptor tropism are likely determinants for the beneficial effect of HPgV-1 co-infection in HIV-1-infected individuals.
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Fama A, Xiang J, Link BK, Allmer C, Klinzman D, Feldman AL, Nowakowski GS, Liebow M, Larson MC, Maurer MJ, Ansell SM, Novak AJ, Asmann YW, Slager SL, Call TG, Habermann TM, Cerhan JR, Stapleton JT. Human Pegivirus infection and lymphoma risk and prognosis: a North American study. Br J Haematol 2018; 182:644-653. [PMID: 29808922 DOI: 10.1111/bjh.15416] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 03/26/2018] [Indexed: 12/12/2022]
Abstract
We evaluated the association of Human Pegivirus (HPgV) viraemia with risk of developing lymphoma, overall and by major subtypes. Because this virus has also been associated with better prognosis in the setting of co-infection with human immunodeficiency virus, we further assessed the association of HPgV with prognosis. We used risk factor data and banked plasma samples from 2094 lymphoma cases newly diagnosed between 2002 and 2009 and 1572 frequency-matched controls. Plasma samples were tested for HPgV RNA by reverse transcription polymerase chain reaction (RT-PCR), and those with RNA concentrations <5000 genome equivalents/ml were confirmed using nested RT-PCR methods. To assess the role of HPgV in lymphoma prognosis, we used 2948 cases from a cohort study of newly diagnosed lymphoma patients (included all cases from the case-control study). There was a positive association of HPgV viraemia with risk of lymphoma overall (Odds ratio = 2·14; 95% confidence interval [CI] 1·63-2·80; P < 0·0001), and for all major subtypes except Hodgkin lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma, and this was not confounded by other lymphoma risk factors. In contrast, there was no association of HPgV viraemia with event-free survival (Hazard ratio [HR] = 1·00; 95% CI 0·85-1·18) or overall survival (HR = 0·97; 95% CI 0·79-1·20) for lymphoma overall, or any of the subtypes. These data support the hypothesis for a role of HPgV in the aetiology of multiple lymphoma subtypes.
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Affiliation(s)
- Angelo Fama
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.,Ematologia, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Jinhua Xiang
- Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
| | - Brian K Link
- Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
| | - Cristine Allmer
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Donna Klinzman
- Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
| | - Andrew L Feldman
- Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA
| | - Grzegorz S Nowakowski
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Mark Liebow
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Melissa C Larson
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Matthew J Maurer
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Stephen M Ansell
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Anne J Novak
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Yan W Asmann
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA
| | - Susan L Slager
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Timothy G Call
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Thomas M Habermann
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - James R Cerhan
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Jack T Stapleton
- Department of Internal Medicine, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
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Tang W, Zhu N, Wang H, Gao Y, Wan Z, Cai Q, Yu S, Tang S. Identification and genetic characterization of equine Pegivirus in China. J Gen Virol 2018; 99:768-776. [PMID: 29658859 DOI: 10.1099/jgv.0.001063] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In 2013, two new viruses, equine pegivirus (EPgV) and Theiler's disease-associated virus (TDAV), both belonging to the genus Pegivirus within the family Flaviviridae, were identified. To investigate the geographical distribution and genetic diversity of these two viruses in China, we screened EPgV and TDAV infection in imported race horses and Chinese work horses by using reverse-transcription polymerase chain reaction (RT-PCR). EPgV was detected in 10.8 % (8/74) of the total horses tested, with a prevalence of 5.8 and 22.7 % in the race horses and work horses, respectively. No TDAV infection was found. A near full-length genome sequence of EPgV was obtained that showed an identity of 89.5-90.6 % at the nucleotide level and 98.1-98.3 % at the amino acid level with an American strain, C0035, and another Chinese strain, LW/216, respectively. Phylogenetic analysis showed two different clusters of the sequences from the race horses and work horses, indicating a difference in virus origin. Our results demonstrated a higher positive rate of EPgV in the Chinese work horses than in the imported race horses, a moderate genetic diversity of EPgV strains worldwide and possibly no liver pathogenesis for EPgV infection.
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Affiliation(s)
- Weiping Tang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Naling Zhu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Haiying Wang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Youwen Gao
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Zhengwei Wan
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Qundi Cai
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Shouyi Yu
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
| | - Shixing Tang
- Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, Guangdong, PR China
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Brennan PN, Donnelly MC, Simpson KJ. Systematic review: non A-E, seronegative or indeterminate hepatitis; what is this deadly disease? Aliment Pharmacol Ther 2018; 47:1079-1091. [PMID: 29468698 DOI: 10.1111/apt.14566] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 10/20/2017] [Accepted: 01/22/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND A significant proportion of cases of acute liver failure (ALF) do not have an identifiable cause; so called "non A-E," "non A, non B, non C," "seronegative" or "indeterminate" hepatitis. However, this entity is clinically not well described. AIM To collate the known incidence and outcomes in indeterminate hepatitis. This systematic review sought to identify potential aetiologies that ought to be considered, and identify likely future objectives in classification and treatment strategies for indeterminate hepatitis. METHODS Literature review to determine aetiological factors, prevalence and outcomes relating to indeterminate hepatitis. RESULTS There is significant heterogeneity within the reported cases of indeterminate hepatitis in the literature. Some of the potential infective aetiologies which are reviewed here include: parvovirus B19 (PVB19), herpes simplex virus (HSV), Toga-Like Virus and the Annelloviridae (including SEN-V). Interestingly, this condition predominately affects middle aged women, with subacute progression of the liver failure. In addition, the prognosis of indeterminate hepatitis is poor, with reduced spontaneous survival compared with other causes of acute liver failure and increased need for emergency liver transplantation. CONCLUSIONS Whilst various pathological processes have been implicated in the development of indeterminate hepatitis, the specific cause remains elusive. There is an urgent need for general consensus on a specific definition and exclusion of confounding aetiologies with coordinated multicentre investigation of this rare condition to identify aetiology and develop therapies to reduce the significant mortality and need for emergency liver transplantation associated with this condition.
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Affiliation(s)
- P N Brennan
- Department of Hepatology and Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - M C Donnelly
- Department of Hepatology and Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - K J Simpson
- Department of Hepatology and Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK
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Hsu JW, Hiemenz JW, Wingard JR, Leather H. Viral Infections in Patients with Hematological Malignancies. NEOPLASTIC DISEASES OF THE BLOOD 2018:1079-1127. [DOI: 10.1007/978-3-319-64263-5_51] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Hayashi S, Tanaka T, Moriishi K, Hirayama K, Yamada A, Hotta K. Seroepidemiology of non-primate hepacivirus (NPHV) in Japanese native horses. J Vet Med Sci 2017; 80:186-189. [PMID: 29187712 PMCID: PMC5797880 DOI: 10.1292/jvms.17-0527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Non-primate hepacivirus (NPHV) is recently identified as a closely related homologue of hepatitis C virus. The previous studies showed a high prevalence of NPHV infection among Japanese domestic horses originated from
abroad. The historical distribution of NPHV among horses in Japan, therefore, is still unknown. In this study, seroepidemiological study of NPHV was conducted using 335 sera from five breeds of Japanese native horses.
These horses are maintained as the pedigree and are reared apart from other horse breeds. The detection of antibodies against NPHV were conducted by western blot analysis using the recombinant protein of the NPHV core
protein. The antibodies against NPHV were detected in all five breeds, 83 out of 335 (23.4%) horses. These results suggested that NPHV was circulating among Japanese native horses.
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Affiliation(s)
- Shizuka Hayashi
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Tomohisa Tanaka
- Department of Microbiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan
| | - Kohji Moriishi
- Department of Microbiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan
| | - Kazuhiro Hirayama
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Akio Yamada
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Kozue Hotta
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
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Singh S, Blackard JT. Human pegivirus (HPgV) infection in sub-Saharan Africa-A call for a renewed research agenda. Rev Med Virol 2017; 27. [PMID: 29148108 DOI: 10.1002/rmv.1951] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 08/26/2017] [Accepted: 08/28/2017] [Indexed: 12/14/2022]
Abstract
The human pegivirus (HPgV)-formerly GB virus C-has a beneficial impact on HIV disease progression that has been described in multiple studies. Given the high prevalence of HIV in sub-Saharan Africa and the continuing need to suppress HIV replication, this review provides a comprehensive overview of the existing data on HPgV infection in sub-Saharan Africa, with a particular focus on studies of prevalence and the circulating HPgV genotypes. This review also highlights the need for additional studies of HPgV conducted on the African continent and proposes a research agenda for evaluation of HPgV.
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Affiliation(s)
- Shivank Singh
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Jason T Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Gonzales-Gustavson E, Timoneda N, Fernandez-Cassi X, Caballero A, Abril JF, Buti M, Rodriguez-Frias F, Girones R. Identification of sapovirus GV.2, astrovirus VA3 and novel anelloviruses in serum from patients with acute hepatitis of unknown aetiology. PLoS One 2017; 12:e0185911. [PMID: 28982120 PMCID: PMC5628893 DOI: 10.1371/journal.pone.0185911] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 09/21/2017] [Indexed: 12/14/2022] Open
Abstract
Hepatitis is a general term meaning inflammation of the liver, which can be caused by a variety of viruses. However, a substantial number of cases remain with unknown aetiology. We analysed the serum of patients with clinical signs of hepatitis using a metagenomics approach to characterize their viral species composition. Four pools of patients with hepatitis without identified aetiological agents were evaluated. Additionally, one pool of patients with hepatitis E (HEV) and pools of healthy volunteers were included as controls. A high diversity of anelloviruses, including novel sequences, was found in pools from patients with hepatitis of unknown aetiology. Moreover, viruses recently associated with gastroenteritis as sapovirus GV.2 and astrovirus VA3 were also detected only in those pools. Besides, most of the HEV genome was recovered from the HEV pool. Finally, GB virus C and human endogenous retrovirus were found in the HEV and healthy pools. Our study provides an overview of the virome in serum from hepatitis patients suggesting a potential role of these viruses not previously described in cases of hepatitis. However, further epidemiologic studies are necessary to confirm their contribution to the development of hepatitis.
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Affiliation(s)
- Eloy Gonzales-Gustavson
- Laboratory of Virus Contaminants of Water and Food, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
| | - N. Timoneda
- Laboratory of Virus Contaminants of Water and Food, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
- Computational Genomics Lab, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain
| | - X. Fernandez-Cassi
- Laboratory of Virus Contaminants of Water and Food, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
| | - A. Caballero
- Hospital Universitari Vall d’Hebron and CIBEREHD del Instituto Carlos III, Barcelona, Catalonia, Spain
| | - J. F. Abril
- Computational Genomics Lab, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain
| | - M. Buti
- Hospital Universitari Vall d’Hebron and CIBEREHD del Instituto Carlos III, Barcelona, Catalonia, Spain
| | - F. Rodriguez-Frias
- Hospital Universitari Vall d’Hebron and CIBEREHD del Instituto Carlos III, Barcelona, Catalonia, Spain
| | - R. Girones
- Laboratory of Virus Contaminants of Water and Food, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
- * E-mail:
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Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing. J Clin Virol 2017; 96:67-72. [PMID: 28992518 DOI: 10.1016/j.jcv.2017.10.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 09/26/2017] [Accepted: 10/01/2017] [Indexed: 01/03/2023]
Abstract
BACKGROUND Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. OBJECTIVES To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. STUDY DESIGN To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. RESULTS Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. CONCLUSIONS This finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF.
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Vitrenko Y, Kostenko I, Kulebyakina K, Sorochynska K. Prevalence of human pegivirus-1 and sequence variability of its E2 glycoprotein estimated from screening donors of fetal stem cell-containing material. Virol J 2017; 14:167. [PMID: 28859680 PMCID: PMC5580293 DOI: 10.1186/s12985-017-0837-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 08/28/2017] [Indexed: 12/16/2022] Open
Abstract
Background Human pegivirus-1 (HPgV-1) is a member of the Flaviviridae family whose genomic organization and mode of cellular entry is similar to that of hepatitis C virus (HCV). The E2 glycoprotein of HPgV-1 is the principle mediator in the virus-cell interaction and as such harbors most of HPgV-1’s antigenic determinants. HPgV-1 persists in blood cell precursors which are increasingly used for cell therapy. Methods We studied HPgV-1 prevalence in a large cohort of females donating fetal tissues for clinical use. PCR was used for screening and estimation of viral load in viremic plasma and fetal samples. Sequence analysis was performed for portions of the 5′-untranslated and E2 regions of HPgV-1 purified from donor plasmas. Sequencing was followed by phylogenetic analysis. Results HPgV-1 was revealed in 13.7% of plasmas, 5.0% of fetal tissues, 5.4% of chorions, exceeding the prevalence of HCV in these types of samples. Transmission of HPgV-1 occurred in 25.8% of traceable mother-chorion-fetal tissues triads. For HPgV-1-positive donors, a high viral load in plasma appears to be a prerequisite for transmission. However, about one third of fetal samples acquired infection from non-viremic individuals. Sequencing of 5′-untranslated region placed most HPgV-1 samples to genotype 2a. At the same time, a portion of E2 sequence provided a much weaker support for this grouping apparently due to a higher variability. Polymorphisms were detected in important structural and antigenic motifs of E2. Conclusion HPgV-1 is efficiently transmitted to fetus at early embryonic stages. A high variability in E2 may pose a risk of generation of pathogenic subtypes. Although HPgV-1 is considered benign and no longer tested mandatorily in blood banks, the virus may have adversary effects at target niches if delivered with infected graft upon cell transplantation. This argues for the necessity of HPgV-1 testing of cell samples aimed for clinical use.
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Kumar A, Murthy S, Kapoor A. Evolution of selective-sequencing approaches for virus discovery and virome analysis. Virus Res 2017; 239:172-179. [PMID: 28583442 PMCID: PMC5819613 DOI: 10.1016/j.virusres.2017.06.005] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 12/28/2016] [Accepted: 06/02/2017] [Indexed: 12/11/2022]
Abstract
Description of virus enrichment techniques for metagenomics based virome analysis. Usefulness of recently developed virome capture sequencing techniques. Perspective on negative and positive selection approaches for virome analysis. Recent advances in sequencing technologies have transformed the field of virus discovery and virome analysis. Once mostly confined to the traditional Sanger sequencing based individual virus discovery, is now entirely replaced by high throughput sequencing (HTS) based virus metagenomics that can be used to characterize the nature and composition of entire viromes. To better harness the potential of HTS for the study of viromes, sample preparation methodologies use different approaches to exclude amplification of non-viral components that can overshadow low-titer viruses. These virus-sequence enrichment approaches mostly focus on the sample preparation methods, like enzymatic digestion of non-viral nucleic acids and size exclusion of non-viral constituents by column filtration, ultrafiltration or density gradient centrifugation. However, recently a new approach of virus-sequence enrichment called virome-capture sequencing, focused on the amplification or HTS library preparation stage, was developed to increase the ability of virome characterization. This new approach has the potential to further transform the field of virus discovery and virome analysis, but its technical complexity and sequence-dependence warrants further improvements. In this review we discuss the different methods, their applications and evolution, for selective sequencing based virome analysis and also propose refinements needed to harness the full potential of HTS for virome analysis.
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Affiliation(s)
- Arvind Kumar
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA
| | - Satyapramod Murthy
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA
| | - Amit Kapoor
- Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210, USA.
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EL Hadad S, Al-Hamdan H, Linjawi S. Partial sequencing analysis of the NS5B region confirmed the predominance of hepatitis C virus genotype 1 infection in Jeddah, Saudi Arabia. PLoS One 2017; 12:e0178225. [PMID: 28552946 PMCID: PMC5446157 DOI: 10.1371/journal.pone.0178225] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/10/2017] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection and its progression are major health problems that many countries including Saudi Arabia are facing. Determination of HCV genotypes and subgenotypes is critical for epidemiological and clinical analysis and aids in the determination of the ideal treatment strategy that needs to be followed and the expected therapy response. Although HCV infection has been identified as the second most predominant type of hepatitis in Saudi Arabia, little is known about the molecular epidemiology and genetic variability of HCV circulating in the Jeddah province of Saudi Arabia. The aim of this study was to determine the dominance of various HCV genotypes and subgenotypes circulating in Jeddah using partial sequencing of the NS5B region. To the best of our knowledge, this is the first study of its kind in Saudi Arabia. To characterize HCV genotypes and subgenotypes, serum samples from 56 patients with chronic HCV infection were collected and subjected to partial NS5B gene amplification and sequence analysis. Phylogenetic analysis of the NS5B partial sequences revealed that HCV/1 was the predominant genotype (73%), followed by HCV/4 (24.49%) and HCV/3 (2.04%). Moreover, pairwise analysis also confirmed these results based on the average specific nucleotide distance identity: ±0.112, ±0.112, and ±0.179 for HCV/1, HCV/4, and HCV/3, respectively, without any interference between genotypes. Notably, the phylogenetic tree of the HCV/1 subgenotypes revealed that all the isolates (100%) from the present study belonged to the HCV/1a subgenotype. Our findings also revealed similarities in the nucleotide sequences between HCV circulating in Saudi Arabia and those circulating in countries such as Morocco, Egypt, Canada, India, Pakistan, and France. These results indicated that determination of HCV genotypes and subgenotypes based on partial sequence analysis of the NS5B region is accurate and reliable for HCV subtype determination.
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Affiliation(s)
- Sahar EL Hadad
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
- Research Center of Genetic Engineering and Bioinformatics, VACSERA, Cairo, Egypt
- * E-mail:
| | - Hesa Al-Hamdan
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sabah Linjawi
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
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Santos LM, Lobato RC, Barral MFM, Gonçalves CV, da Hora VP, Martinez AMB. Prevalence and vertical transmission of human pegivirus among pregnant women infected with HIV. Int J Gynaecol Obstet 2017; 138:113-118. [PMID: 28391635 DOI: 10.1002/ijgo.12175] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Revised: 02/25/2017] [Accepted: 04/06/2017] [Indexed: 11/07/2022]
Abstract
OBJECTIVE To determine the prevalence of human pegivirus (HPgV) and factors associated with vertical transmission among pregnant women infected with HIV. METHOD A retrospective cross-sectional study was conducted among pregnant women treated at an HIV reference service in Rio Grande, Brazil, between January 1, 2010, and January 1, 2015. The polymerase chain reaction was used to diagnose HPgV infection among the women and their neonates. Clinical, obstetric, and neonatal data were obtained from medical records. RESULTS Infection with HPgV was detected among 16 (25%) of 63 women and 5 (8%) of 63 newborns, corresponding to a vertical transmission rate of 31%. Multivariate analysis demonstrated that the absence of prenatal care was the only risk factor for vertical transmission of HPgV (prevalence ratio 19.61, 95% confidence interval 1.29-297.48; P=0.032). CONCLUSION Prenatal care could protect against vertical transmission of HPgV among women infected with HIV; however, studies among HIV-negative individuals are still required to verify this correlation.
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Affiliation(s)
- Lucas M Santos
- Laboratory of Molecular Biology, University Hospital, Universidade Federal do Rio Grande, Rio Grande, Brazil
| | - Rubens C Lobato
- Laboratory of Molecular Biology, University Hospital, Universidade Federal do Rio Grande, Rio Grande, Brazil
| | - Maria Fernanda M Barral
- Laboratory of Molecular Biology, University Hospital, Universidade Federal do Rio Grande, Rio Grande, Brazil
| | - Carla V Gonçalves
- Medicine Faculty, University Hospital, Universidade Federal do Rio Grande, Rio Grande, Brazil
| | - Vanusa P da Hora
- Laboratory of Molecular Biology, University Hospital, Universidade Federal do Rio Grande, Rio Grande, Brazil
| | - Ana Maria B Martinez
- Laboratory of Molecular Biology, University Hospital, Universidade Federal do Rio Grande, Rio Grande, Brazil
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Ben Dhifallah I, Ayouni K, Chouiha A, Sadraoui A, Hogga N, Hammami W, Ben Yahya A, Triki H. Genotype Distribution and Prevalence of Human Pegivirus among High-Risk Populations in Tunisia. Intervirology 2017; 59:170-178. [PMID: 28132064 DOI: 10.1159/000454810] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 11/25/2016] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE A recently discovered non-A-E hepatitis virus has been designated as human Pegivirus (HPgV). HPgV is prevalent in high-risk groups such as patients with hepatitis C virus (HCV), and it is of interest for patients who are at risk for transmitted infections. The aim of this study was to evaluate the prevalence of HPgV as well as the genotype distribution among patients in the Tunisian population who are infected with HCV and also in multitransfused patients. METHODS A total of 144 patients were screened using RTPCR/nested PCR of the 5'-untranslated region (UTR); 14 cases were sequenced and phylogenetically analyzed. RESULTS Seven (14.9%) subjects from the multitransfused group and 7 (7.2%) patients infected with HCV, respectively, were found positive for HPgV RNA. Sequencing and phylogenetic analysis of the 14 cases revealed that genotype 2a was the main genotype circulating in Tunisian patients. Genotype 2b was found in the amplified samples of 2 HCV-infected patients. CONCLUSION This study enriches the limited data on HPgV prevalence in Tunisia, and shows, for the first time, the molecular epidemiology of the circulating strains in this country.
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Treatment of hepatitis C in renal impairment and renal transplant. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2016. [DOI: 10.1007/s40506-016-0089-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Poovorawan Y, Theamboonlers A, Chongsrisawat V, Seksarn P. Post-hepatitis aplastic anaemia: causal link to viral hepatitis A to G? ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 2016. [DOI: 10.1080/00034983.1997.11813166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Poovorawan Y, Theamboonlers A, Chongsrisawat V, Jantaradsamee P. Prevalence of infection with hepatitis G virus among various groups in Thailand. ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 2016. [DOI: 10.1080/00034983.1998.11813265] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Smith DB, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff AS, Pletnev A, Rico-Hesse R, Stapleton JT, Simmonds P. Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family. J Gen Virol 2016; 97:2894-2907. [PMID: 27692039 PMCID: PMC5770844 DOI: 10.1099/jgv.0.000612] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (family Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A–N) and 11 Pegivirus species (Pegivirus A–K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences for members of each proposed taxon. We propose that the species Hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimize confusion. Despite the newly documented genetic diversity of hepaciviruses and pegiviruses, members of these genera remain phylogenetically distinct, and differ in hepatotropism and the possession of a basic core protein; pegiviruses in general lack these features. However, other characteristics that were originally used to support their division into separate genera are no longer definitive; there is overlap between the two genera in the type of internal ribosomal entry site and the presence of miR-122 sites in the 5′ UTR, the predicted number of N-linked glycosylation sites in the envelope E1 and E2 proteins, the presence of poly U tracts in the 3′ UTR and the propensity of viruses to establish a persistent infection. While all classified hepaciviruses and pegiviruses have mammalian hosts, the recent description of a hepaci-/pegi-like virus from a shark and the likely existence of further homologues in other non-mammalian species indicate that further species or genera remain to be defined in the future.
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Affiliation(s)
- Donald B Smith
- Centre for Immunity, Infection and Evolution, University of Edinburgh, Scotland, UK
| | - Paul Becher
- Institute of Virology, University of Veterinary Medicine, Hannover, Germany
| | - Jens Bukh
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.,Copenhagen Hepatitis C Program (CO-HEP), Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Ernest A Gould
- EHESP French School of Public Health, French Institute of Research for Development (IRD), Aix Marseille Université, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France
| | - Gregor Meyers
- Institut für Immunologie, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany
| | - Thomas Monath
- Hookipa Biotech AG, Vienna, Austria.,PaxVax Inc., Menlo Park and Redwood City, CA, USA
| | - A Scott Muerhoff
- Abbott Diagnostics Research and Development, Abbott Park, IL, USA
| | - Alexander Pletnev
- Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Rebecca Rico-Hesse
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Jack T Stapleton
- Medical Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA.,Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.,Department of Microbiology, University of Iowa, Iowa City, IA, USA
| | - Peter Simmonds
- Centre for Immunity, Infection and Evolution, University of Edinburgh, Scotland, UK.,Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Mirvish ED, Shuda M. Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction. Front Microbiol 2016; 7:676. [PMID: 27242703 PMCID: PMC4865503 DOI: 10.3389/fmicb.2016.00676] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 04/26/2016] [Indexed: 01/07/2023] Open
Abstract
Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.
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Affiliation(s)
- Ezra D Mirvish
- Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh PA, USA
| | - Masahiro Shuda
- Cancer Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh PA, USA
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Viral metagenomics applied to blood donors and recipients at high risk for blood-borne infections. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2016; 14:400-7. [PMID: 27136432 DOI: 10.2450/2016.0160-15] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 01/18/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Characterisation of human-associated viral communities is essential for epidemiological surveillance and to be able to anticipate new potential threats for blood transfusion safety. In high-resource countries, the risk of blood-borne agent transmission of well-known viruses (HBV, HCV, HIV and HTLV) is currently considered to be under control. However, other unknown or unsuspected viruses may be transmitted to recipients by blood-derived products. To investigate this, the virome of plasma from individuals at high risk for parenterally and sexually transmitted infections was analysed by high throughput sequencing (HTS). MATERIALS AND METHODS Purified nucleic acids from two pools of 50 samples from recipients of multiple transfusions, and three pools containing seven plasma samples from either HBV-, HCV- or HIV-infected blood donors, were submitted to HTS. RESULTS Sequences from resident anelloviruses and HPgV were evidenced in all pools. HBV and HCV sequences were detected in pools containing 3.8×10(3) IU/mL of HBV-DNA and 1.7×10(5) IU/mL of HCV-RNA, respectively, whereas no HIV sequence was found in a pool of 150 copies/mL of HIV-RNA. This suggests a lack of sensitivity in HTS performance in detecting low levels of virus. In addition, this study identified other issues, including laboratory contaminants and the uncertainty of taxonomic assignment of short sequence. No sequence suggestive of a new viral species was identified. DISCUSSION This study did not identify any new blood-borne virus in high-risk individuals. However, rare and/or viruses present at very low titre could have escaped our protocol. Our results demonstrate the positive contribution of HTS in the detection of viral sequences in blood donations.
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Miyamura T. Global Control of Hepatitis C Virus Infection. HEPATITIS C VIRUS II 2016:347-368. [DOI: 10.1007/978-4-431-56101-9_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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