Enterovirus A71 2C Mediates Lipolysis Of Lipid Droplets

Enterovirus A71 can cause hand,foot and mouth disease,which is an infectious disease that occurs more frequently in infants and young children and has received widespread attention worldwide.The patient's hands,feet and buttocks will have blisters,accompanied by high fever symptoms.The disease is usually mild and self-limiting,but may involve severe and life-threatening neurological symptoms and cardiopulmonary complications.Currently,there are no multivalent vaccines or antiviral drugs for hand,foot and mouth disease.Enterovirus A71 is a single-stranded positive-strand RNA virus.Like other positive-strand RNA viruses,its genome replication occurs on rearranged membrane structures called replication compartments.Because the viral protein 2C is beneficial to the formation of replication compartments,it plays an important role in the process of viral replication.Therefore,the study of host proteins that interact with 2C can help us better understand the process of viral replication.Preliminary mass spectrometry analysis revealed the host factors of enterovirus A71 2C:TRIM4,Exportin2 and ARFGAP1.We found that TRIM4,Exportin2 and ARFGAP1 interact with 2C and affect virus replication.In studying the interaction between TRIM4 and 2C,we found an interesting phenomenon that EV-A71 2C will form a loop when expressed in 293T cells.Studies have shown that the poliovirus protein 2C has lipid droplets localization and clusters LDs.However,the relationship between enterovirus A71 and lipid droplets is unclear.This study found that several enterovirus proteins 2C can be localized in lipid droplets and cluster lipid droplets.When 2C is expressed alone in the 293T cell line,lipid droplets are also degraded to some extent,and the surface protein ADRP of lipid droplets will dissociate.In addition,knocking down ADRP increases the amount of enterovirus A71 genomic RNA inside and outside the cell.Therefore,ADRP may be involved in the process of lipolysis of lipid droplets regulated by the viral protein 2C.This study enriches the mechanism of host cytokines in enterovirus A71 replication,and provides new ideas for finding potential drug targets for enterovirus A71.