Reprogramming of lipid metabolism by ORF3a-induced microlipophagy enhances biogenesis of SARS-CoV-2 replication organelle.

ABSTRACT: Infection by positive-strand RNA viruses necessitates membrane expansion and elevated phospholipid biosynthesis, whereby fatty acids stored as triacylglycerols in lipid droplets (LDs) are mobilized to promote metabolic processes and membrane biogenesis. The replication organelles (ROs) of coronavirus associate with modified host endomembrane; however, the molecular mechanisms underlying the expansion and modification of these membranes remain poorly understood. Here, we show that viral protein orf3a collaborates with nsp3, nsp4, nsp6 to facilitate the formation of ROs in SARS-CoV-2. Importantly, orf3a targets LDs to ROs, establishing novel membrane contact sites and induces host cell microlipophagy, which supplies essential lipids for RO biogenesis. Subsequently, Following the formation of

SUBMITTER: Li Z 

PROVIDER: S-EPMC12671888 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature