Hepatitis C virus (HCV) and human pegivirus (GB virus C) are globally distributed and infect 2- 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 their virus homologs in small mammals, including wild rodents. Results of our ongoing studies identify, for the first time, several new species of hepaciviruses (HCV-like viruses) and pegiviruses (GBV-like viruses) in wild rodents. The presence of genes, encoded proteins and translation elements homologous to those found in human viruses, lead us to hypothesize that these different rodent virus species resemble HCV or GBV-C in their biological properties. The proposed genetic and biological characterization of these novel rodent viruses will enable the development of tractable animal models with which to study virus-host interactions and may culminate in new strategies for therapeutic intervention. We propose two specific aims:
Aim -1: Identify rodent HCV and GBV-C like viruses (HGLVs) and characterize their complete genomes, natural host and species tropism;
and Aim -2: Investigate HGLV infection, tissue tropism and pathogenesis using experimental infections of natural host animal species. Pursuit of these aims will lead to identification of the new rodent HGLV species that are similar to their human homologs in tissue tropism and pathogenesis. Results of our studies will open up new avenues of research on HCV and GBV-C like viruses, and will help in identifying virus and host factors that determine hepacivirus and pegivirus tissue and species tropism, persistence, virulence, immune escape and pathogenesis.

Public Health Relevance

An estimated 2% and 1-5% of the world's population is chronically infected with hepatitis C virus and GBV-C viruses, respectively. We will identify and characterize rodent homologs of these important human viruses and develop tractable animal models to study virus-host interactions. Our studies will provide new insight into the biology of these viruses paving the way for development of strategies to prevent their infection and diseases

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI107631-01A1
Application #
8638384
Study Section
Virology - A Study Section (VIRA)
Program Officer
Koshy, Rajen
Project Start
2014-01-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$202,703
Indirect Cost
$64,869
Name
Columbia University (N.Y.)
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032