Identification of Rodent Homologs of Hepatitis C Virus and Pegiviruses

被引:157
作者
Kapoor, Amit [1 ]
Simmonds, Peter [2 ]
Scheel, Troels K. H. [3 ,4 ,5 ,6 ]
Hjelle, Brian [7 ]
Cullen, John M. [8 ]
Burbelo, Peter D. [9 ]
Chauhan, Lokendra V. [1 ]
Duraisamy, Raja [1 ]
Leon, Maria Sanchez [1 ]
Jain, Komal [1 ]
Vandegrift, Kurt Jason [10 ]
Calisher, Charles H. [1 ]
Rice, Charles M. [3 ]
Lipkin, W. Ian [1 ]
机构
[1] Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA
[2] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland
[3] Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA
[4] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program CO HEP, Dept Infect Dis, Hvidovre, Denmark
[5] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark
[6] Univ Copenhagen, Fac Hlth & Med Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark
[7] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA
[8] North Carolina Coll Vet Med, Raleigh, NC USA
[9] Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, NIH, Bethesda, MD USA
[10] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA
来源
MBIO | 2013年 / 4卷 / 02期
基金
英国生物技术与生命科学研究理事会; 美国国家卫生研究院;
关键词
SURROGATE MODEL; INFECTION; GENOMES; REPLICATION; NUCLEOTIDE; PERSISTENT; CULTURE; SYSTEM; ENTRY;
D O I
10.1128/mBio.00216-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:10
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