Direct and Indirect Effects on Viral Translation and RNA Replication Are Required for AUF1 Restriction of Enterovirus Infections in Human Cells.

摘要: The cellular mRNA decay protein AUF1 acts as a restriction factor during infection by picornaviruses, including poliovirus, coxsackievirus, and human rhinovirus. relocalizes from the nucleus to cytoplasm these viruses due disruption of nucleocytoplasmic trafficking viral proteinases. Previous studies have demonstrated that binds poliovirus coxsackievirus B3 (CVB3) RNA infection, with binding shown occur within internal ribosome entry site (IRES) 5' noncoding region (NCR) or 3' NCR, respectively. Binding different sites suggests may negatively regulate using mechanisms. work presented here addresses mechanism inhibition replication CVB3. We demonstrate knockdown in cells results increased translation, synthesis, virus production. is translation CVB3 IRES reporter but not uninfected cells. found this inhibitory activity mediated through destabilization genomic RNA; however, it does require virus-induced relocalization early phases infection. Our findings suggest uses common IRES, which distinct canonical role plays regulated host cells.IMPORTANCE Picornaviruses primarily infect gastrointestinal upper respiratory tracts humans animals disseminate tissues central nervous system, heart, skin, liver, pancreas. Many pathogens belong Picornaviridae family, includes known cause paralytic poliomyelitis (poliovirus); myocarditis (coxsackievirus [CVB3]); cold (human rhinovirus [HRV]); hand, foot, mouth disease (enterovirus 71 [EV71]), among other illnesses. There are no specific treatments for vaccines exist only two picornaviruses: hepatitis A virus. Given worldwide distribution prevalence important gain insight into mechanisms used restrict Other than proteins involved innate immune response, few factors been identified picornavirus replication. seeks define action