Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Middle East Respiratory Syndrome Coronavirus-Encoded Accessory Proteins Impair MDA5-and TBK1-Mediated Activation of NF-κB

  • Lee, Jeong Yoon (Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material Science, Chonbuk National University) ;
  • Bae, Sojung (Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material Science, Chonbuk National University) ;
  • Myoung, Jinjong (Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material Science, Chonbuk National University)
  • Received : 2019.08.01
  • Accepted : 2019.08.13
  • Published : 2019.08.28
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Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging coronavirus which is zoonotic from bats and camels. Its infection in humans can be fatal especially in patients with preexisting conditions due to smoking and chronic obstructive pulmonary disease (COPD). Among the 25 proteins encoded by MERS-CoV, 5 accessory proteins seem to be involved in viral evasion of the host immune responses. Here we report that ORF4a, ORF4b, and ORF8b proteins, alone or in combination, effectively antagonize nuclear factor kappa B ($NF-{\kappa}B$) activation. Interestingly, the inhibition of $NF-{\kappa}B$ by MERS-CoV accessory proteins was mostly at the level of pattern recognition receptors: melanoma differentiation-associated gene 5 (MDA5). ORF4a and ORF4b additively inhibit MDA5-mediated activation of $NF-{\kappa}B$ while that of retinoic acid-inducible gene 1 (RIG-I) is largely not perturbed. Of note, ORF8b was found to be a novel antagonist of MDA5-mediated $NF-{\kappa}B$ activation. In addition, ORF8b also strongly inhibits Tank-binding kinase 1 (TBK1)-mediated induction of $NF-{\kappa}B$ signaling. Taken together, MERS-CoV accessory proteins are involved in viral escape of $NF-{\kappa}B$-mediated antiviral immune responses.

Keywords

References

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