Deciphering the role of lipid droplets in Hepatitis C virus replication

• Applicant: Professorin Dr. Eva Herker
• Subject Area: Virology
• Term: from 2013 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 248680339

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and is one of the leading causes of liver-related morbidity and mortality. HCV infection as well as replication of the virus is closely tied to the lipid metabolism of infected hepatocytes. About half of all individuals chronically infected with HCV develop fatty liver disease, a condition characterized by the massive accumulation of lipid droplets in infected cells. Intriguingly, lipid droplets also emerged as crucial organelles for HCV infection, particularly for assembly of viral progeny. However, why the virus requires lipid droplets for replication as well as the mechanistic details of the late steps of HCV replication remain ill defined. Our goal is to elucidate in molecular detail the role of lipid droplets in HCV infection and pathogenesis. We have previously shown that host proteins involved in lipid droplet biogenesis and function serve as key regulators of viral replication. We then compared lipid droplet-associated proteins in HCV-infected versus control cells and identified candidate proteins that may serve as host-dependency or -restriction factors that will be now studied in molecular detail. Functional annotation suggests that HCV infection causes a disconnection of lipid droplets from metabolic function and/or regulation. The experiments proposed here will decipher molecular mechanisms and temporal/spatial coordination of HCV assembly, maturation, and egress. In addition they will further elucidate the function of lipid droplets in HCV replication and pathogenesis.

• DFG Programme: Research Grants