Lipid-mediated control of immune responses in hepatitis C virus infection

University Of Virginia, Charlottesville VA

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): Hepatitis C is a serious health concern that affects 3% of the world's population and leads to the development of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma. The causative agent of hepatitis C is the hepatitis C virus (HCV). Despite recent advances in the treatment of chronic HCV infection, liver damage continues to persist even after clearance of virus. Previous studies have demonstrated that HCV relies on lipids for its propagation, which results in distinct metabolic changes in infected patients. In this study, we will examine the relationship among host lipid metabolism, virus production, and the immune response. Our preliminary studies using small molecule inhibitors of acetyl-CoA carboxylase, the rate-limiting enzyme for fatty acid synthesis, suggest that inhibition of de novo lipogenesis has a significant impact on HCV replication. Lipidomics, microscopy, and a variety of molecular biology, virology, and immunology techniques will be used to further define how changes in lipids impact viral propagation and modulate the immune response in HCV- infected hepatocytes and macrophages exposed to the virus. Results from this study may uncover new roles for specific lipids in HCV infection and identify potential links between metabolism and the immune response. Collectively, these results may not only propel the development of therapies based on lipid metabolism, but also provide a more complex understanding of other chronic inflammatory diseases.