AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase

Hand,foot and mouth disease(HFMD),mainly caused by enterovirus 71(EV71),has frequently occurred in the Asia-Pacific region,posing a significant threat to the health of infants and young children.Therefore,research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important.The 3D polymerase,as the most critical RNA-dependent RNA polymerase(RdRp)for EV71 replication,is widely targeted to inhibit EV71 infection.In this study,we identified a novel host protein,AIMP2,capable of binding to 3D polymerase and inhibiting EV71 infection.Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2,which mediates the polyubiquitination and degradation of 3D polymerase.Furthermore,the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes.Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection,revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.

ANXA2 Facilitates Enterovirus 71 Infection by Interacting with 3D Polymerase and PI4KB to Assist the Assembly of Replication Organelles

Similar to that of other enteroviruses, the replication of enterovirus 71(EV71) occurs on rearranged membranous structures called replication organelles(ROs). Phosphatidylinositol 4-kinase Ⅲ(PI4KB), which is required by enteroviruses for RO formation, yields phosphatidylinositol-4-phosphate(PI4P) on ROs. PI4P then binds and induces conformational changes in the RNA-dependent RNA polymerase(Rd Rp) to modulate Rd Rp activity. Here, we targeted 3D polymerase, the core enzyme of EV71 ROs, and found that the host factor Annexin A2(ANXA2) can interact with 3 D polymerase and promote the replication of EV71. Then, an experiment showed that the annexin domain of ANXA2, which possesses membranebinding capacity, mediates the interaction of ANXA2 with EV71 3 D polymerase. Further research showed that ANXA2 is localized on ROs and interacts with PI4KB. Overexpression of ANXA2 stimulated the formation of PI4P, and the level of PI4P was decreased in ANXA2-knockout cells. Furthermore, ANXA2, PI4KB, and 3D were shown to be localized to the viral RNA replication site, where they form a higher-order protein complex, and the presence of ANXA2 promoted the PI4 KB-3D interaction. Altogether, our data provide new insight into the role of ANXA2 in facilitating formation of the EV71 RNA replication complex.

Dyngo-4a protects mice from rotavirus infection by affecting the formation of dynamin 2 oligomers

Rotavirus is the most common etiologic agent of severe diarrhea in infants and young children and causes more than 200,000 deaths annually worldwide[1,2].Licensed rotavirus vaccines can provide more than 50%protection against rotavirus infection,and currently available etiological treatments for rotavirus gastroenteritis mainly involve the use of oral rehydration solution and zinc supplementation[3].However,targeted interventions are in great need for rotavirus-induced gastroenteritis control.