The Mechanistic Study On COPI Promoting EV71 Virus Proliferation

Enterovirus71(EV71),an Enterovirus in the family Picornaviridae,has become the main pathogen responsible for hand-foot-and-mouth disease in children.Little has been known about EV71 replication,which appears to be unique among picornaviruses.In this study we found that COPI,a protein complex coating vesicles required for the formation of virus replication complex,was involved in EV71 replication.?'-COP,a COPI component,and viral double-stranded RNA co-localized in speckle-like structures in EV71-infected cells.In p-COP knockdown cells,the number of speckle-like structures decreased with reduced dsRNA.Treatment of cells with Brefeldin A,which prevents COPI from membrane binding and formation of COPI-coated vesicles,resulted in significant inhibition of viral replication along with decreased speckle-like structures.Interestingly,COPI co-localized with lipid droplets,on which the speckle-like structures were based.When formation of lipid droplets was inhibited,COPI activity was restrained,suggesting that COPI is associated with lipid droplets and involved in EV71 replication.Furthermore,we found that viral 2C protein co-localized with lipid droplets and interacted with ?'-COP,indicating that 2C may play an important role in recruiting COPI into lipid droplets for EV71 replication complex formation.These findings may suggest a new mechanism associated with lipid metabolism for EV71 replication.