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Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε.
Wong, Lok-Yin Roy; Ye, Zi-Wei; Lui, Pak-Yin; Zheng, Xuyang; Yuan, Shuofeng; Zhu, Lin; Fung, Sin-Yee; Yuen, Kit-San; Siu, Kam-Leung; Yeung, Man-Lung; Cai, Zongwei; Woo, Patrick Chiu-Yat; Yuen, Kwok-Yung; Chan, Chi-Ping; Jin, Dong-Yan.
  • Wong LR; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • Ye ZW; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
  • Lui PY; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • Zheng X; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • Yuan S; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
  • Zhu L; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
  • Fung SY; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • Yuen KS; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • Siu KL; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
  • Yeung ML; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
  • Cai Z; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
  • Woo PC; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
  • Yuen KY; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
  • Chan CP; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong; chancp10@hku.hk dyjin@hku.hk.
  • Jin DY; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong; chancp10@hku.hk dyjin@hku.hk.
J Immunol ; 205(6): 1564-1579, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-694818
ABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV-infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-ß expression induced by Sendai virus and poly(IC). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-ß expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-ß induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Interferon Type I / Enzyme Activation / I-kappa B Kinase / Middle East Respiratory Syndrome Coronavirus Limits: Humans Language: English Journal: J Immunol Year: 2020 Document Type: Article Affiliation country: Jimmunol.1901489

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Proteins / Interferon Type I / Enzyme Activation / I-kappa B Kinase / Middle East Respiratory Syndrome Coronavirus Limits: Humans Language: English Journal: J Immunol Year: 2020 Document Type: Article Affiliation country: Jimmunol.1901489