Remodelled cholesteryl ester enriched lipid droplets fuel flavivirus morphogenesis.

ABSTRACT: Flaviviruses such as dengue and Zika viruses extensively remodel host cell membranes to create specialised replication organelles, but the role of lipid metabolism to generate them remain poorly understood. Through systematic screens of fatty acyl transferase enzymes (MBOAT and zDHHC families) and complementary approaches including CRISPR/Cas9 gene deletions, pharmacological inhibition, proteomics, and photo-crosslinkable cholesterol analogues, we identified cholesteryl ester-enriched lipid droplets (CE-LDs) as critical host components required for flavivirus infection. CE-LD formation is mediated by Sterol O-acyltransferases 1 and 2 (SOAT1/SOAT2), whose activities were upregulated early during infection, coinciding with increased CE-LD formation and transition to liquid crystalline phases

SUBMITTER: Banducci-Karp A 

PROVIDER: S-EPMC12645520 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature