Identification of rodent homologs of hepatitis C virus and pegiviruses

TY - JOUR

T1 - Identification of rodent homologs of hepatitis C virus and pegiviruses

AU - Kapoor, Amit

AU - Simmonds, Peter

AU - Scheel, Troels K H

AU - Hjelle, Brian

AU - Cullen, John M

AU - Burbelo, Peter D

AU - Chauhan, Lokendra V

AU - Duraisamy, Raja

AU - Sanchez Leon, Maria

AU - Jain, Komal

AU - Vandegrift, Kurt Jason

AU - Calisher, Charles H

AU - Rice, Charles M

AU - Lipkin, W Ian

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Animals

KW - Cluster Analysis

KW - Flaviviridae

KW - Genetic Variation

KW - Genome, Viral

KW - Molecular Sequence Data

KW - Peromyscus

KW - Phylogeny

KW - RNA, Viral

KW - Sequence Analysis, DNA

KW - Sigmodontinae

U2 - 10.1128/mBio.00216-13

DO - 10.1128/mBio.00216-13

M3 - Journal article

C2 - 23572554

SN - 2161-2129

VL - 4

SP - e00216-13

JO - mBio

JF - mBio

IS - 2

ER -