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10.4049/jimmunol.1901489

http://scihub22266oqcxt.onion/10.4049/jimmunol.1901489
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32747502!9202338!32747502
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suck abstract from ncbi


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pmid32747502      J+Immunol 2020 ; 205 (6): 1564-1579
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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 IKKepsilon #MMPMID32747502
  • Wong LR; Ye ZW; Lui PY; Zheng X; Yuan S; Zhu L; Fung SY; Yuen KS; Siu KL; Yeung ML; Cai Z; Woo PC; Yuen KY; Chan CP; Jin DY
  • J Immunol 2020[Sep]; 205 (6): 1564-1579 PMID32747502show ga
  • 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-beta expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKepsilon and chaperone protein HSP70, which is required for the activation of IKKepsilon 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 IKKepsilon. Ectopic expression of HSP70 relieved suppression of IFN-beta expression by ORF8b in an IKKepsilon-dependent manner. Enhancement of IFN-beta induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKepsilon activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKepsilon for interaction with HSP70.
  • |Betacoronavirus[MESH]
  • |COVID-19[MESH]
  • |Cell Line[MESH]
  • |Coronavirus Infections[MESH]
  • |Enzyme Activation/*immunology[MESH]
  • |HSP70 Heat-Shock Proteins/immunology/metabolism[MESH]
  • |Humans[MESH]
  • |I-kappa B Kinase/*immunology/metabolism[MESH]
  • |Interferon Type I/*immunology/metabolism[MESH]
  • |Middle East Respiratory Syndrome Coronavirus/*immunology/metabolism[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral[MESH]
  • |SARS-CoV-2[MESH]


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