Hepatitis C virus (HCV) is a major world-wide cause of chronic liver disease and hepatic failure for which effective therapies are needed. Within the positive-strand RNA genome of HCV exists an internal ribosomal entry site (IRES) that mediates viral gene expression. Significant efforts have been directed toward characterization of HCV IRES-mediated translation initiation, partly because the HCV IRES presents an attractive target for antiviral therapy. However, a role for specific c^-acting HCV RNA elements in translation control and the function of trans-acting cellular proteins in this process remains obscure. This application examines the molecular mechanism of translation initiation at the HCV IRES and its modulation by the 3' nontranslated region, the polypyrimidine tract binding protein, and previously unidentified trans-acting factors. Cis- and trans-acting regulatory factors will be characterized through the utilization of a novel cellbased reporter expression system that takes into account the complex involvement of viral and cellular determinants in translation control at the HCV IRES. ? ?

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 #
1F32DK067781-01A2
Application #
6999666
Study Section
Special Emphasis Panel (ZRG1-F13 (20))
Program Officer
Podskalny, Judith M,
Project Start
2005-12-01
Project End
2008-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
1
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Duke University
Department
Genetics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Bradrick, Shelton S; Dobrikova, Elena Y; Kaiser, Constanze et al. (2007) Poly(A)-binding protein is differentially required for translation mediated by viral internal ribosome entry sites. RNA 13:1582-93
Bradrick, Shelton S; Walters, Robert W; Gromeier, Matthias (2006) The hepatitis C virus 3'-untranslated region or a poly(A) tract promote efficient translation subsequent to the initiation phase. Nucleic Acids Res 34:1293-303