Hepatitis C virus (HCV) often causes persistent infection in humans, which may lead to progressive liver disease. We hypothesize that disease progression from chronic HCV infection is attributed, at least in part, to the effect of HCV core protein on the expression of host cellular genes. Our long term goal is to understand the underlying mechanisms behind HCV mediated liver disease progression. We were among the first to identify many intriguing functions related to HCV core protein, which may significantly contribute to disease progression. However, there are critical gaps in our understanding of the key cellular targets and molecular mechanisms by which core protein exerts these functions alone or in context to other HCV proteins. HCV induces hepatocellular insulin resistance and hepatic fibrogenesis. Our focus in this grant application is to examine the underlying mechanisms of HCV induced insulin resistance and fibrogenesis as a follow up to our preliminary data provided with this application. The current research proposal includes complementary but independent aims to address our hypothesis.
Aim 1 will investigate the mechanism of IRS phosphorylation by HCV core protein, Aim 2 will investigate the functional correlates of HCV core protein induced metabolic regulators, and Aim 3 will evaluate the role of HCV core protein in hepatic fibrosis. Studies will also be performed using full-length cDNA, replicon or cell culture grown HCV to provide a molecular basis for HCV core protein functions in context to other HCV proteins. Knowledge on the molecular determinants involved in HCV mediated disease progression will open avenues for novel therapeutic approach.

Public Health Relevance

Hepatitis C virus (HCV) often causes persistent infection and progressive liver disease. We plan to understand the molecular determinants involved in HCV mediated liver disease progression, which will open avenues for novel therapeutic approach.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Hepatobiliary Pathophysiology Study Section (HBPP)
Program Officer
Doo, Edward
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Saint Louis University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
Zip Code
Shrivastava, Shubham; Devhare, Pradip; Sujijantarat, Nanthiya et al. (2016) Knockdown of Autophagy Inhibits Infectious Hepatitis C Virus Release by the Exosomal Pathway. J Virol 90:1387-96
Kwon, Young-Chan; Kim, Hangeun; Meyer, Keith et al. (2016) Distinct CD55 Isoform Synthesis and Inhibition of Complement-Dependent Cytolysis by Hepatitis C Virus. J Immunol 197:1127-36
Kwon, Young-Chan; Bose, Sandip K; Steele, Robert et al. (2015) Promotion of Cancer Stem-Like Cell Properties in Hepatitis C Virus-Infected Hepatocytes. J Virol 89:11549-56
Meyer, Keith; Kwon, Young-Chan; Liu, Shuanghu et al. (2015) Interferon-α inducible protein 6 impairs EGFR activation by CD81 and inhibits hepatitis C virus infection. Sci Rep 5:9012
Kim, Hangeun; Ray, Ranjit (2014) Evasion of TNF-α-mediated apoptosis by hepatitis C virus. Methods Mol Biol 1155:125-32
Kim, Hangeun; Bose, Sandip K; Meyer, Keith et al. (2014) Hepatitis C virus impairs natural killer cell-mediated augmentation of complement synthesis. J Virol 88:2564-71
Mukherjee, Anupam; Shrivastava, Shubham; Bhanja Chowdhury, Joydip et al. (2014) Transcriptional suppression of miR-181c by hepatitis C virus enhances homeobox A1 expression. J Virol 88:7929-40
Bose, Sandip K; Kim, Hangeun; Meyer, Keith et al. (2014) Forkhead box transcription factor regulation and lipid accumulation by hepatitis C virus. J Virol 88:4195-203
Kim, Hangeun; Meyer, Keith; Di Bisceglie, Adrian M et al. (2014) Inhibition of c3 convertase activity by hepatitis C virus as an additional lesion in the regulation of complement components. PLoS One 9:e101422
Bose, Sandip K; Ray, Ranjit (2013) Association of lipid droplet and hepatitis C virus proteins: insights for virus replication. J Lipid Res 54:871-2

Showing the most recent 10 out of 19 publications