Enterovirus 71 Regulates EGR1 Expression That In Turn To Stimulates Viral Replication

Enterovirus 71(EV71) infection causes a variety of diseases,ranging from herpangina, HFMD(hand,foot and mouth disease),menigoencephalitis, aseptic meningitis, to fatal encephalitis. Unfortunately, due to lacking understanding viral replication,multiple serotypes, antigenic variation and genomic mutations,there is no effective treatment for EV71 infection. Early growth response-1(EGRl) is a classical zinc finger protein with multifunction in regulating the expression of many genes involved in neuronal plasticity,inflammation, apoptosis,differentiation,and tumourigenesis. Here,we determined the correlation between EV71 infection and EGRl expression and the role of EGRl in virus replication. EGRl expression is regulated by EV71 infection: in the early phase of infection,EV71 activates EGRl expression through regulating the PKA, PKCs and PI3K/Akt signaling cascades by enhancing the phosphorylation of the signaling components,while in the late phase of infection,EV71 induces EGRl protein nonspecific degradation through viral proteases evoked cell apoptosis and caspase activity. More interestingly, EGRl directly binds to the stem-loops I and IV in 5,untranslated region(5'UTR) of EV71 RNA tiirough its first two zinc fingers. After EV71 infection, the cellular EGRl protein and the viral RNA are co-localized in the cytoplasm of virus-infected cells to facilitate viral production, EV71 internal ribosomal entry site(IRES) activity,viral protein expression and RNA synthesis.In addition, EGRl can activate EV71 replication excluding miR-141 effect Thus,our findings provided new insights into the mechanism underling EV71 replication and pathogenesis, and revealed a new role of EGRl in regulating EV71 replication and infection.