Heterogeneous nuclear ribonucleoprotein A3 binds to the internal ribosomal entry site of enterovirus A71 and affects virus replication in neural cells

Abstract

Enterovirus A71 (EV‐A71) belongs to the genus Enterovirus of the Picornaviridae family and often causes outbreaks in Asia. EV‐A71 infection usually causes hand, foot, and mouth disease and can even affect the central nervous system, causing neurological complications or death. The 5′‐untranslated region (5′‐UTR) of EV‐A71 contains an internal ribosome entry site (IRES) that is responsible for the translation of viral proteins. IRES‐transacting factors can interact with the EV‐A71 5′‐UTR to regulate IRES activity. Heterogeneous nuclear ribonucleoprotein (hnRNP) A3 is a member of the hnRNP A/B protein family of RNA‐binding proteins and is involved in RNA transport and modification. We found that hnRNP A3 knockdown promoted the replication of EV‐A71 in neural calls. Conversely, increasing the expression of hnRNP A3 within cells inhibits the growth of EV‐A71. HnRNP A3 can bind to the EV‐A71 5′‐UTR, and knockdown of hnRNP A3 enhances the luciferase activity of the EV‐A71 5′‐UTR IRES. The localization of hnRNP A3 shifts from the nucleus to the cytoplasm of infected cells during viral infection. Additionally, EV‐A71 infection can increase the protein expression of hnRNP A3, and the protein level is correlated with efficient viral growth. Based on these findings, we concluded that hnRNP A3 plays a negative regulatory role in EV‐A71 replication within neural cells.