It is estimated that 170 million people worldwide are infected with hepatitis C virus (HCV). HCV infection routinely results in chronic hepatitis that may progress over time to further liver disease, including cirrhosis and hepatocellular carcinoma. Chronic HCV infection is one of the leading risk factors associated with endstage liver disease and subsequent liver transplantation. Overall, our understanding of the viral-host interactions in vivo is severely limited. The inability to produce live virus in culture, combined with the lack of a reliable small animal model, have impeded progress in determining exactly how HCV contributes to liver disease pathology. Understanding where HCV is located, and in what cell types infection occurs, is critical to deciphering many unknown aspects of the HCV life cycle; however detecting sites of replication remains a major challenge. The objective of this proposal is to provide unequivocal in situ data regarding HCV site of replication, determine if an in vivo association exists with proliferating cell populations, and analyze viral effects on cellular gene expression, in order to provide greater insight into the mechanisms of pathogenesis in HCV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK070497-01
Application #
6883883
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Podskalny, Judith M,
Project Start
2005-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Rockefeller University
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
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Walters, Kathie-Anne; Syder, Andrew J; Lederer, Sharon L et al. (2009) Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes. PLoS Pathog 5:e1000269
Lindenbach, Brett D; Meuleman, Philip; Ploss, Alexander et al. (2006) Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 103:3805-9
Lindenbach, Brett D; Evans, Matthew J; Syder, Andrew J et al. (2005) Complete replication of hepatitis C virus in cell culture. Science 309:623-6