Deciphering the function of lipid droplet subsets in flavivirus infection

• Applicant: Professorin Dr. Eva Herker
• Subject Area: Virology ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 538651361

Several flaviviruses depend on host lipid droplets (LDs) for replication. 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 1) the analysis of the functional role of nuclear and cytoplasmic LDs in ZIKV infection, 2) the investigation of the LD coat proteins PLIN2 and PLIN3 in orthoflavivirus infection, and 3) the study of LD membrane contact site formation and dynamics in orthoflavivirus-infected cells.

• DFG Programme: Research Units
• Subproject of: FOR 5815: Structural and functional lipid droplet heterogeneity