Abstract

Chronic infection by hepatitis C virus (HCV) is the leading cause of severe hepatitis, which often develops into liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms underlying HCV replication and pathogenesis are poorly understood. The identity of host or viral proteins relevant to the state of liver disease associated with HCV infection is not known. Although we have recently identified various cellular factors that interact with HCV 3'NTR (Appendix #1), nothing is known about the components of the HCV replication complex. These components are expected to have crucial roles in the production of infectious HCV virions. We have devised a means of capturing the replication complex in situ from HCV-infected cells and identifying its components by proteomics technology. We will investigate the implication of each identified cellular component on HCV replication by siRNA-mediated genetic knockdown of its expression in the cells. This will yield valuable information about the identity of the cellular or viral factors associated with the replication complex and facilitate the identity of new targets for use in preventing the viral infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI073703-02
Application #
7828015
Study Section
Special Emphasis Panel (ZRG1-IDM-K (91))
Program Officer
Koshy, Rajen
Project Start
2009-05-07
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$234,000
Indirect Cost

  Institution

Name
University of Medicine & Dentistry of NJ
Department
Biochemistry
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107

  Publications

Mishra, Priya; Dixit, Updesh; Pandey, Ashutosh K et al. (2017) Modulation of HCV replication and translation by ErbB3 binding protein1 isoforms. Virology 500:35-49
Dixit, Updesh; Pandey, Ashutosh K; Mishra, Priya et al. (2016) Staufen1 promotes HCV replication by inhibiting protein kinase R and transporting viral RNA to the site of translation and replication in the cells. Nucleic Acids Res 44:5271-87
Manvar, Dinesh; Singh, Kamlendra; Pandey, Virendra N (2013) Affinity labeling of hepatitis C virus replicase with a nucleotide analogue: identification of binding site. Biochemistry 52:432-44
Upadhyay, Alok; Dixit, Updesh; Manvar, Dinesh et al. (2013) Affinity capture and identification of host cell factors associated with hepatitis C virus (+) strand subgenomic RNA. Mol Cell Proteomics 12:1539-52
Manvar, Dinesh; Mishra, Mahesh; Kumar, Suriender et al. (2012) Identification and evaluation of anti hepatitis C virus phytochemicals from Eclipta alba. J Ethnopharmacol 144:545-54