Hepatitis C virus induced dysregulation of lipid metabolism and implications for HCC development (A02)

• Subject Area: Virology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314905040

Project A02 (Lohmann/Bartenschlager; Hepatitis C virus induced dysregulation of lipid metabolism and implications for HCC development) addresses the procarcinogenic mechanism of HCV with specific emphasis on the disturbance of lipid homeostasis. It has demonstrated that HCV infection alters the abundance and subcellular distribution of signalling lipids, especially phosphatidic acid (PA), which supports the biogenesis of membranous HCV replication organelles, promotes selective autophagy, fibrosis and HCC development. It has furthermore shown that HCV-induced Phosphatidylinositol-4-kinase IIIα (PI4KA) has protumorigenic activity. The project will now determine hepatocarcinogenic mechanisms of HCV-induced lipotoxicity by identifying PA-binding proteins by targeted proteomics and identifying the effects of PI4KA on the cytoskeleton with regard to invasiveness and metastasis, thus paving a way for potential intervention.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 209: Liver Cancer - New mechanistic and therapeutic concepts in a solid tumor model
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Ralf Friedrich Wilhelm Bartenschlager; Professor Dr. Volker Lohmann