Novel exploitation of autophagy by tombusviruses.

Abstract

Positive-strand (+)RNA viruses are major pathogens of humans, animals and plants. This review summarizes the complex interplay between the host autophagy pathway and Tomato bushy stunt virus (TBSV) replication. Recent discoveries with TBSV have revealed virus-driven exploitation of autophagy in multiple ways that contributes to the unique phospholipid composition of viral replication organellar (VROs) membranes. Viral replication protein-driven subversion of phagophore membranes, recruitment of ATG2 bulk lipid transfer protein to enrich phosphatidylethanolamine and phosphatidylserine in VROs, recruitment of VPS34 PI3K to produce PI(3)P; and ATG11-facilitated formation of stable viral membrane contact sites contributes to VRO membrane proliferation. Recruitment of autophagy core proteins to vir-NBR1 bodies within vir-condensates associated with VROs results in dampened antiviral degradation by autophagy. Overall, TBSV intricate interplay with the autophagy machinery highlights the importance of lipid dynamics in viral life cycles and points toward potential directions for therapeutic intervention.