Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses

ABSTRACT Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity, and pat...

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Autores principales: Amit Kapoor, Peter Simmonds, Troels K. H. Scheel, Brian Hjelle, John M. Cullen, Peter D. Burbelo, Lokendra V. Chauhan, Raja Duraisamy, Maria Sanchez Leon, Komal Jain, Kurt Jason Vandegrift, Charles H. Calisher, Charles M. Rice, W. Ian Lipkin
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Publicado: American Society for Microbiology 2013
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spelling oai:doaj.org-article:921e00488ea046188be72ef946ac07cc2021-11-15T15:40:26ZIdentification of Rodent Homologs of Hepatitis C Virus and Pegiviruses10.1128/mBio.00216-132150-7511https://doaj.org/article/921e00488ea046188be72ef946ac07cc2013-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00216-13https://doaj.org/toc/2150-7511ABSTRACT Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity, and pathogenesis. To address this challenge, we searched for homologous viruses in small mammals, including wild rodents. Here we report the discovery of several new hepaciviruses (HCV-like viruses) and pegiviruses (GB virus-like viruses) that infect wild rodents. Complete genome sequences were acquired for a rodent hepacivirus (RHV) found in Peromyscus maniculatus and a rodent pegivirus (RPgV) found in Neotoma albigula. Unique genomic features and phylogenetic analyses confirmed that these RHV and RPgV variants represent several novel virus species in the Hepacivirus and Pegivirus genera within the family Flaviviridae. The genetic diversity of the rodent hepaciviruses exceeded that observed for hepaciviruses infecting either humans or non-primates, leading to new insights into the origin, evolution, and host range of hepaciviruses. The presence of genes, encoded proteins, and translation elements homologous to those found in human hepaciviruses and pegiviruses suggests the potential for the development of new animal systems with which to model HCV pathogenesis, vaccine design, and treatment. IMPORTANCE The genetic and biological characterization of animal homologs of human viruses provides insights into the origins of human infections and enhances our ability to study their pathogenesis and explore preventive and therapeutic interventions. Horses are the only reported host of nonprimate homologs of hepatitis C virus (HCV). Here, we report the discovery of HCV-like viruses in wild rodents. The majority of HCV-like viruses were found in deer mice (Peromyscus maniculatus), a small rodent used in laboratories to study viruses, including hantaviruses. We also identified pegiviruses in rodents that are distinct from the pegiviruses found in primates, bats, and horses. These novel viruses may enable the development of small-animal models for HCV, the most common infectious cause of liver failure and hepatocellular carcinoma after hepatitis B virus, and help to explore the health relevance of the highly prevalent human pegiviruses.Amit KapoorPeter SimmondsTroels K. H. ScheelBrian HjelleJohn M. CullenPeter D. BurbeloLokendra V. ChauhanRaja DuraisamyMaria Sanchez LeonKomal JainKurt Jason VandegriftCharles H. CalisherCharles M. RiceW. Ian LipkinAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 2 (2013)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Amit Kapoor
Peter Simmonds
Troels K. H. Scheel
Brian Hjelle
John M. Cullen
Peter D. Burbelo
Lokendra V. Chauhan
Raja Duraisamy
Maria Sanchez Leon
Komal Jain
Kurt Jason Vandegrift
Charles H. Calisher
Charles M. Rice
W. Ian Lipkin
Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
description ABSTRACT Hepatitis C virus (HCV) and human pegivirus (HPgV or GB virus C) are globally distributed and infect 2 to 5% of the human population. The lack of tractable-animal models for these viruses, in particular for HCV, has hampered the study of infection, transmission, virulence, immunity, and pathogenesis. To address this challenge, we searched for homologous viruses in small mammals, including wild rodents. Here we report the discovery of several new hepaciviruses (HCV-like viruses) and pegiviruses (GB virus-like viruses) that infect wild rodents. Complete genome sequences were acquired for a rodent hepacivirus (RHV) found in Peromyscus maniculatus and a rodent pegivirus (RPgV) found in Neotoma albigula. Unique genomic features and phylogenetic analyses confirmed that these RHV and RPgV variants represent several novel virus species in the Hepacivirus and Pegivirus genera within the family Flaviviridae. The genetic diversity of the rodent hepaciviruses exceeded that observed for hepaciviruses infecting either humans or non-primates, leading to new insights into the origin, evolution, and host range of hepaciviruses. The presence of genes, encoded proteins, and translation elements homologous to those found in human hepaciviruses and pegiviruses suggests the potential for the development of new animal systems with which to model HCV pathogenesis, vaccine design, and treatment. IMPORTANCE The genetic and biological characterization of animal homologs of human viruses provides insights into the origins of human infections and enhances our ability to study their pathogenesis and explore preventive and therapeutic interventions. Horses are the only reported host of nonprimate homologs of hepatitis C virus (HCV). Here, we report the discovery of HCV-like viruses in wild rodents. The majority of HCV-like viruses were found in deer mice (Peromyscus maniculatus), a small rodent used in laboratories to study viruses, including hantaviruses. We also identified pegiviruses in rodents that are distinct from the pegiviruses found in primates, bats, and horses. These novel viruses may enable the development of small-animal models for HCV, the most common infectious cause of liver failure and hepatocellular carcinoma after hepatitis B virus, and help to explore the health relevance of the highly prevalent human pegiviruses.
format article
author Amit Kapoor
Peter Simmonds
Troels K. H. Scheel
Brian Hjelle
John M. Cullen
Peter D. Burbelo
Lokendra V. Chauhan
Raja Duraisamy
Maria Sanchez Leon
Komal Jain
Kurt Jason Vandegrift
Charles H. Calisher
Charles M. Rice
W. Ian Lipkin
author_facet Amit Kapoor
Peter Simmonds
Troels K. H. Scheel
Brian Hjelle
John M. Cullen
Peter D. Burbelo
Lokendra V. Chauhan
Raja Duraisamy
Maria Sanchez Leon
Komal Jain
Kurt Jason Vandegrift
Charles H. Calisher
Charles M. Rice
W. Ian Lipkin
author_sort Amit Kapoor
title Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
title_short Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
title_full Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
title_fullStr Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
title_full_unstemmed Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
title_sort identification of rodent homologs of hepatitis c virus and pegiviruses
publisher American Society for Microbiology
publishDate 2013
url https://doaj.org/article/921e00488ea046188be72ef946ac07cc
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