Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses
Open Access
- 1 May 2013
- journal article
- Published by American Society for Microbiology in mBio
- Vol. 4 (2), e00216-13
- https://doi.org/10.1128/mbio.00216-13
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.This publication has 38 references indexed in Scilit:
- Serology-Enabled Discovery of Genetically Diverse Hepaciviruses in a New HostJournal of Virology, 2012
- Hepatitis C homolog in dogs with respiratory illnessProceedings of the National Academy of Sciences of the United States of America, 2011
- Characterization of a canine homolog of hepatitis C virusProceedings of the National Academy of Sciences of the United States of America, 2011
- The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family FlaviviridaeJournal of General Virology, 2010
- Use of Nucleotide Composition Analysis To Infer Hosts for Three Novel Picorna-Like VirusesJournal of Virology, 2010
- Multiple novel astrovirus species in human stoolJournal of General Virology, 2009
- GB virus type C interactions with HIV: the role of envelope glycoproteinsJournal of Viral Hepatitis, 2009
- Human occludin is a hepatitis C virus entry factor required for infection of mouse cellsNature, 2009
- A highly prevalent and genetically diversified Picornaviridae genus in South Asian childrenProceedings of the National Academy of Sciences of the United States of America, 2008
- Production of infectious hepatitis C virus in tissue culture from a cloned viral genomeNature Medicine, 2005