[Feb. 5]Advanced Seminar Series

 Advanced Seminar Series「Enterovirus RNA synthesis: the flux of lipids into the membranous replication complex」

Positive-stranded RNA viruses extensively remodel host cell architecture to enable viral replication. Here we examined the poorly understood formation of specialized membrane compartments which are critical sites for the synthesis of the viral genome. We show that the replication compartments (RCs) of enteroviruses are created through novel membrane contact sites that recruit host lipid droplets (LDs) to the RCs. Highly conserved viral proteins physically tether the RCs to the LDs and interact with the host lipolysis machinery to enable the efficient transfer of fatty acids from LDs, thereby providing lipids essential for RC biogenesis. Inhibiting the formation of the membrane contact sites between LDs and RCs or inhibition of the lipolysis pathway disrupts RC biogenesis and enterovirus replication. Our data illuminate mechanistic and functional aspects of organelle remodeling in viral infection and establish that pharmacological targeting of contact sites linking viral and host compartments is a potential strategy for antiviral development.

Prof. Raul Andino

Department of Microbiology and Immunology, University of California San Francisco