Enterovirus 71 Inhibits Typical Stress Granule Formation By Disrupting EIF4GI-G3BP Interaction

Enterovirus 71(EV71)belongs to the genus Enterovirus in the family of Picornaviridae,which also includes coxsackievirus,poliovirus(PV),and human rhinovirus.EV71 can cause hand-foot-mouth disease that can result in death.Stress granules(SG)are non-membranous,transiently assembled cytoplasmic aggregates of 48 S m RNPs and associated proteins,where stalled translation preinitiation complexes(PICs)repress the translation of nonessential m RNAs and modulate cell signaling by sequestering key signal proteins.A variety of environmental stresses,including viral infection,can trigger SG formation in eukaryotic cells.Virus infection imposes stress on host cells and thereby induces SG formation and SG can shut off the translation of bulk m RNAs to regulate gene expression and compartmentalization of heterologous viral RNAs and proteins.To antagonize host defense,many viruses have evolved various strategies to disruptSG formation for releasing transcripts of their proteins.We previously found that 2A protease of picornaviruses blocks typical stress granules(tSG)formation and induces atypical stress granules(a SG)formation,but the molecular mechanism by which 2A protease inhibits tSG formation remains unclear.Here,we found that the interaction of eukaryotic translation initiation factor 4 gamma I(eIF4GI)is critical for tSG formation by interacting with Ras-GTPase-activating protein SH3-domain-binding protein(G3BP),and this interaction is mediated by aa 182-203 of eIF4 GI.Upon eIF4GI-G3 BP interaction,eIF4 GI can assemble into tSG and rescue tSG formation.Furthermore,we found that 2A protease of EV71 inhibits tSG formation by disrupting the interaction of eIF4 GI and G3 BP.In conclusion,we provide the first evidence that the interaction of eIF4 GI and G3 BP is necessary for tSG formation,and 2A protease of EV71 can disrupt eIF4GI-G3 BP interaction,thereby blocking tSG formation.