There is no robust cell culture system in which the hepatitis C virus (HCV) can replicate. As such, surrogate models of HCV replication are frequently used for the evaluation of antiviral compounds. The GB virus B (GBV-B) is the closest related virus phylogenetically with HCV and is an attractive surrogate model for HCV drug development efforts. Unfortunately, GBV-B can so far only be grown in primary hepatocytes taken from small non-human primates. This makes the current GBV-B antiviral assay difficult to perform, expensive, and not amenable to high-throughput (HTP) screening. This application aims to develop a robust cell culture model of GBV-B replication utilizing immortalized cell lines.
The specific aims of this project are to immortalize the primary hepatocytes of GBV-B-susceptible animals, identify if these and other established cell lines can support GBV-B replication in vitro, and to standardize and validate the model system produced for use in the evaluation of antiviral agents. This project will make the GBV-B antiviral assay widely available, affordable, and appropriate for HTP applications. This will facilitate the discovery and development of new anti-HCV drugs that may improve the quality of life for HCV-infected patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI053574-02
Application #
6661917
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Koshy, Rajen
Project Start
2002-09-19
Project End
2005-09-30
Budget Start
2003-09-19
Budget End
2005-09-30
Support Year
2
Fiscal Year
2003
Total Cost
$114,920
Indirect Cost
Name
Southern Research Institute
Department
Type
DUNS #
006900526
City
Birmingham
State
AL
Country
United States
Zip Code
35205
Buckwold, Victor E; Collins, Barbara; Hogan, Priscilla et al. (2005) Investigation into the ability of GB virus B to replicate in various immortalized cell lines. Antiviral Res 66:165-8
Huang, Zhuhui; Buckwold, Victor E (2005) A TaqMan PCR assay using degenerate primers for the quantitative detection of woodchuck hepatitis virus DNA of multiple genotypes. Mol Cell Probes 19:282-9
Buckwold, Victor E; Wilson, Richard J H; Nalca, Aysegul et al. (2004) Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res 61:57-62
Buckwold, Victor E (2004) Implications of finding synergic in vitro drug-drug interactions between interferon-alpha and ribavirin for the treatment of hepatitis C virus. J Antimicrob Chemother 53:413-4
Buckwold, Victor E; Wei, Jiayi; Wenzel-Mathers, Michelle et al. (2003) Synergistic in vitro interactions between alpha interferon and ribavirin against bovine viral diarrhea virus and yellow fever virus as surrogate models of hepatitis C virus replication. Antimicrob Agents Chemother 47:2293-8
Buckwold, Victor E; Beer, Brigitte E; Donis, Ruben O (2003) Bovine viral diarrhea virus as a surrogate model of hepatitis C virus for the evaluation of antiviral agents. Antiviral Res 60:1-15