Proviral role of ATG2 autophagy related protein in tomato bushy stunt virus replication through bulk phospholipid transfer into the viral replication organelle

• Published in: Molecular biology of the cell Vol. 35; no. 10; p. mbcE24050236
• Main Authors: Kang, Yuanrong, Pogany, Judit, Nagy, Peter D
• Format: Journal Article
• Language: English
• Published: United States 01.10.2024
• ISSN: 1059-1524; 1939-4586; 1939-4586
• DOI: 10.1091/mbc.E24-05-0236

Subversion of cellular membranes and membrane proliferation are used by positive-strand RNA viruses to build viral replication organelles (VROs) that support virus replication. The biogenesis of the membranous VROs requires major changes in lipid metabolism and lipid transfer in infected cells. In this work, we show that tomato bushy stunt virus (TBSV) hijacks Atg2 autophagy related protein with bulk lipid transfer activity into VROs via interaction with TBSV p33 replication protein. Deletion of Atg2 in yeast and knockdown of Atg2 in resulted in decreased TBSV replication. We found that subversion of Atg2 by TBSV was important to enrich VRO membranes with phosphatidylethanolamine (PE), phosphatidylserine (PS) and PI(3)P phosphoinositide. Interestingly, inhibition of authophagy did not affect efficient recruitment of Atg2 into VROs and over-expression of Atg2 enhanced TBSV replication, indicating autophagy-independent subversion of Atg2 by TBSV. These findings suggest that the pro-viral function of Atg2 lipid transfer protein is in VRO membrane proliferation. In addition, we find that Atg2 interacting partner Atg9 with membrane lipid scramblase activity is also co-opted for tombusvirus replication. Altogether, subversion of Atg2 bridge-type lipid transfer protein provides a new mechanism for tombusviruses to greatly expand VRO membranes to support robust viral replication.