Co-opted ATG2 lipid transfer protein delivers phospholipids for biogenesis of viral replication organelles

Positive-strand RNA viruses, which are important pathogens of humans, animals and plants, subvert cellular membranes and induce de novo membrane proliferation to generate viral replication organelles (VROs) that support virus replication. Tomato bushy stunt virus (TBSV), an extensively-studied plant virus replicating in yeast model host and plants, hijacks ATG2 (autophagy-related 2), a lipid transfer protein (LTP) that transports lipids between adjacent organelles at membrane contact sites, for the biogenesis of their membranous VROs. Subversion of ATG2 by TBSV is important to enrich VRO membranes with phosphatidylethanolamine (PE), phosphatidylserine (PS) and the phosphoinositide phosphatidylinositol-3-phosphate [PI(3)P], which are all required for viral replication. TBSV replication protein directly interacts with ATG2 leading to recruitment to VRO membranes independently of the autophagy machinery.