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Article: Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε

TitleMiddle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε
Authors
KeywordsBetacoronavirus
cell line
Coronavirus infection
enzyme activation
human
Issue Date2020
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal of Immunology, 2020, v. 205 n. 6, p. 1564-1579 How to Cite?
AbstractMiddle 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-β 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 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-β expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-β 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.
Persistent Identifierhttp://hdl.handle.net/10722/286746
ISSN
2020 Impact Factor: 5.422
2015 SCImago Journal Rankings: 3.549
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, LYR-
dc.contributor.authorYe, Z-
dc.contributor.authorLui, PY-
dc.contributor.authorZheng, X-
dc.contributor.authorYuan, S-
dc.contributor.authorZhu, L-
dc.contributor.authorFung, SY-
dc.contributor.authorYuen, KS-
dc.contributor.authorSiu, KL-
dc.contributor.authorYeung, ML-
dc.contributor.authorCai, Z-
dc.contributor.authorWoo, PCY-
dc.contributor.authorYuen, KY-
dc.contributor.authorChan, CP-
dc.contributor.authorJin, D-
dc.date.accessioned2020-09-04T13:29:44Z-
dc.date.available2020-09-04T13:29:44Z-
dc.date.issued2020-
dc.identifier.citationJournal of Immunology, 2020, v. 205 n. 6, p. 1564-1579-
dc.identifier.issn0022-1767-
dc.identifier.urihttp://hdl.handle.net/10722/286746-
dc.description.abstractMiddle 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-β 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 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-β expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-β 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.-
dc.languageeng-
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org-
dc.relation.ispartofJournal of Immunology-
dc.subjectBetacoronavirus-
dc.subjectcell line-
dc.subjectCoronavirus infection-
dc.subjectenzyme activation-
dc.subjecthuman-
dc.titleMiddle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε-
dc.typeArticle-
dc.identifier.emailYe, Z: zwye@hku.hk-
dc.identifier.emailZheng, X: mushiabc@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailFung, SY: kittyfsy@connect.hku.hk-
dc.identifier.emailYuen, KS: samyuen@HKUCC-COM.hku.hk-
dc.identifier.emailSiu, KL: sklsfx@hkucc.hku.hk-
dc.identifier.emailYeung, ML: pmlyeung@hku.hk-
dc.identifier.emailWoo, PCY: pcywoo@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChan, CP: chancp10@hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityYeung, ML=rp01402-
dc.identifier.authorityWoo, PCY=rp00430-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChan, CP=rp02031-
dc.identifier.authorityJin, D=rp00452-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.4049/jimmunol.1901489-
dc.identifier.pmid32747502-
dc.identifier.scopuseid_2-s2.0-85091125773-
dc.identifier.hkuros313927-
dc.identifier.volume205-
dc.identifier.issue6-
dc.identifier.spage1564-
dc.identifier.epage1579-
dc.identifier.isiWOS:000567623300010-
dc.publisher.placeUnited States-
dc.identifier.issnl0022-1767-

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