Project P7
Deciphering the function of lipid droplet subsets in flavivirus infection
Several flaviviruses depend on host lipid droplets (LDs) for replication (Herker, FEBS letters, 2024). In preliminary experiments, we observed that capsid proteins from different flaviviruses localize to spatially distinct LDs. Our goal is to assess how targeting specific LD subsets facilitates efficient viral replication. We will elucidate the molecular mechanism, timing, and functional relevance of the interaction of orthoflavivirus proteins with LD subsets (nuclear vs cytoplasmic; PLIN2- vs PLIN3-coated LDs). Further, we plan to investigate the consequence of specifically targeting LD subsets for lipid mobilization, a process required for generating membranous viral replication organelles (ROs) and for envelope formation of infectious viral particles, as well as for metabolizing lipids as an energy source for virus multiplication. Our objectives are
the analysis of the functional role of LD subsets in orthoflavivirus infection,
the investigation of the LD coat proteins PLIN2 and PLIN3 in orthoflavivirus infection, and
the study of LD membrane contact site formation and dynamics in orthoflavivirus-infected cells.