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KMID : 0545120180280111908
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Journal of Microbiology and Biotechnology
2018 Volume.28 No. 11 p.1908 ~ p.1915
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Hepatitis E Virus Papain-Like Cysteine Protease Inhibits Type I Interferon Induction by Down-Regulating Melanoma Differentiation-Associated Gene 5
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Kim Eun-Ha
Myoung Jin-Jong
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Abstract
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Upon viral infection, the host cell recognizes the invasion through a number of pattern recognition receptors. Melanoma differentiation associated gene 5 (MDA5) and retinoic acidinducible gene-I (RIG-I) recognize RNA molecules derived from invading viruses, activating down-stream signaling cascades, culminating in the induction of the type I interferon. On the other hand, viruses have evolved to evade type I interferon-mediated inhibition. Hepatitis E virus has been shown to encode a few antagonists of type I interferon and it is not surprising that viruses encode multiple mechanisms of viral evasion. In the present study, we demonstrated that HEV PCP strongly down-regulates MDA5-mediated activation of interferon β induction in a dose-dependent manner. Interestingly, MDA5 protein expression was almost completely abolished. In addition, polyinosinic polycytidylic acid (poly(I:C))- and Sendai virus-mediated activation of type I interferon responses were similarly abrogated in the presence of HEV PCP. Furthermore, HEV PCP down-regulates several molecules that play critical roles in the induction of type I IFN expression. Taken together, these data collectively suggest that HEV-encoded PCP is a strong antagonist of type I interferon.
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KEYWORD
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Hepatitis E virus, type I interferon, interferon beta, MDA5
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