Principal Investigator
Dr. Gabrielle Vieyres
Universität zu Lübeck
B3.2
PhD candidate
Muhammad Nadeem
B3.2
Project Summary
Interplay between Hepatitis C Virus and the hepatic lipid droplet mosaic
Hepatitis C Virus (HCV) infection is closely linked to steatosis and profound remodeling of host lipid metabolism. Moreover, HCV tightly depends on hepatic lipid droplets (LDs) for its replication cycle. The emerging concept of LD heterogeneity, still poorly understood in liver cells, suggests that the virus might exploit and/or perturb specific LD subpopulations for assembly, persistence, and pathogenesis.
The goal of this project is to define hepatic LD subsets at the physical, molecular, and functional levels and to determine how HCV selectively hijacks these subsets during infection. To this end, the work will (i) identify LD subsets in naïve and infected liver-derived cells, (ii) biochemically characterize HCV-coated versus non-coated LDs, and (iii) unravel the functional contribution of defined LD subsets to the HCV replication cycle and pathogenesis.
Liver-derived cell lines (e.g., Huh hepatoma cells) will be endogenously edited with fluorescently tagged candidate LD subset markers, combined with recombinant HCV systems expressing epitope-tagged core and NS5A to visualize viral protein–LD interactions at single-droplet resolution. Automated image analysis, LD isolation, and affinity purification or flow cytometry–based single-organelle sorting, followed by proteomics and lipidomics, will be used to map the protein and lipid composition of distinct LD subsets and their remodeling by HCV. By integrating imaging, proteomic, lipidomic, and functional infection assays, my project aims to uncover LD subset-specific machineries and LDs that are either required for or restrict HCV replication. Defining how HCV manipulates or avoids particular LD subsets will not only refine the concept of LD speciation in hepatocytes but might also reveal new targets and pathways relevant for virus-induced steatosis, metabolic-dysfunction-associated steatohepatitis, and hepatocellular carcinoma.
B3.2