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

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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.