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.
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|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|
|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; 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|
|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|