Abstract
Enterovirus 71 (EV71) is the causative pathogen of hand, foot, and mouth disease (HFMD). However, no effective antiviral therapy is currently available. Some viruses could escape the host's innate immunity by upregulating suppressor of cytokine signaling (SOCS) proteins. Until now, whether EV71 evades the host immune system by regulating the expression of SOCS proteins remains unknown. In this study, we found that EV71 infection promoted SOCS expression at both mRNA and protein levels in vitro and in vivo. Consistently, the infectivity of EV71 was decreased significantly in the SOCS3 or SOCS1 knockdown cells, suggesting that SOCS1 and especially SOCS3 are crucial for EV71 infection. Further investigation showed that SOCS3 promoted virus infection by inhibiting interferon-induced STAT3 phosphorylation. SOCS1 and SOCS3 mRNA expressions were independent on virus-induced type I interferon expression but were blocked by the inhibitor of NF-κB. Therefore, EV71 infection stimulates the expression of SOCS proteins in an interferon-independent way and negatively regulates the JAK/STAT signaling pathway, thus escaping host immunity. All these results may add new information to the mechanism of EV71 in fighting against type I interferon responses.
Highlights
Enterovirus 71 (EV71), a member of the Picornavirus family, is notable for its role in epidemics of hand, foot, and mouth disease (HFMD) in children, which is a global infectious disease that affects millions of people [1]
To examine whether the expressions of suppressor of cytokine signaling (SOCS) proteins are affected by EV71 infection, RD cells were infected with the EV71 virus and the mRNA levels of SOCS1 and SOCS3 were tested by RT-PCR
The results showed that SOCS1 and SOCS3 mRNA levels increased in the early stages of EV71 infection (Figures 1(a) and 1(b))
Summary
Enterovirus 71 (EV71), a member of the Picornavirus family, is notable for its role in epidemics of hand, foot, and mouth disease (HFMD) in children, which is a global infectious disease that affects millions of people [1]. Virus infection can induce a large number of antiviral factors and host immune responses [3, 4]. The type I interferon (IFN) (including IFNα and IFNβ) system is a first line of the defense against viral infections [5]. Type I IFN can induce the production of various antiviral factors through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway [6]. When IFN binds to IFN receptors (IFNAR1 and IFNAR2) on the cell surface, JAK, which is linked to IFNAR1 and IFNAR2, is recruited and activated by phosphorylation. STATs form heterodimers after binding to phosphorylated IFNAR1.
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