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Middle East Respiratory Syndrome Coronavirus-Encoded ORF8b Inhibits RIG-I-Like Receptors by a Differential Mechanism

김성준|명진종|이정윤
한국미생물·생명공학회 (The Korean Society For Microbiology And Biotechnology)|2019.12|Journal of Microbiology and Biotechnology|제29권 제12호|pp. 2014-2021|DOI 10.4014/jmb.1911.11024

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MERS-CoVinterferonRIG-I
주제분류생물학

초록

Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/ RIG-I receptor signaling pathway.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/ RIG-I receptor signaling pathway.

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관련 논문AI추천

Middle East Respiratory Syndrome Coronavirus-Encoded Accessory Proteins Impair MDA5-and TBK1-Mediated Activation of NF-κB명진종, 배소정, 이정윤한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2019 · 제29권 제8호Dengue Virus 2 NS2B Targets MAVS and IKKε to Evade the Antiviral Innate Immune ResponseChen Jinzhi, Deng Dongqing, Long Qizhou, Mou Lumin, Nie Ying, Wu Jiahong한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2023 · 제33권 제5호Hepatitis E Virus Papain-Like Cysteine Protease Inhibits Type I Interferon Induction by Down-Regulating Melanoma Differentiation-Associated Gene 5김은하, 명진종한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2018 · 제28권 제11호Zika Virus Proteins NS2A and NS4A Are Major Antagonists that Reduce IFN-β Promoter Activity Induced by the MDA5/RIG-I Signaling Pathway김성준, 명진종, 이정윤, Nguyen Thi Thuy Ngan한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2019 · 제29권 제10호Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I강상민, 권요셉, 김성준, 노성운, 명진종, 박미경, 최인수, 최종선, 최창순, 한귀남한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2018 · 제28권 제9호Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing이종수, Chathuranga Kiramage, Dodantenna Niranjan, Weerawardhana Asela생화학분자생물학회 · Experimental and Molecular Medicine2021 · 제53권

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