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

Journal of Microbiology and Biotechnology 2019년 29권 12호 p.2014 ~ 2021
이정윤 ( Lee Jeong-Yoon ) - Chonbuk National University Department of Bioactive Material Sciences

김성준 ( Kim Seong-Jun ) - Korea Research Institute of Chemical Technology Center for Convergent Research of Emerging Virus Infection
명진종 ( Myoung Jin-Jong ) - Chonbuk National University Department of Bioactive Material Sciences

Abstract


Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the beta coronavirus subfamily and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such 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 seem 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, 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.

키워드

MERS-CoV; interferon; RIG-I
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