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Article: Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus

TitleHuman tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus
Authors
Issue Date2018
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal of Clinical Investigation, 2018, v. 128 n. 11, p. 5163-5177 How to Cite?
AbstractEnterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ–inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-γ–treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-γ for EV-A71 infection. Given that we detected high levels of IFN-γ in patients with severe EV-A71 infection, our findings extend the knowledge of the pathogenicity of EV-A71 in relation to entry factor expression upon IFN-γ stimulation and the therapeutic options for treating severe EV-A71–associated complications.
Persistent Identifierhttp://hdl.handle.net/10722/274575
ISSN
2019 Impact Factor: 11.864
2015 SCImago Journal Rankings: 8.764
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYeung, ML-
dc.contributor.authorJia, L-
dc.contributor.authorYip, CY-
dc.contributor.authorChan, JFW-
dc.contributor.authorTeng, LL-
dc.contributor.authorChan, KH-
dc.contributor.authorCai, J-
dc.contributor.authorZhang, C-
dc.contributor.authorZhang, J-
dc.contributor.authorWong, LWM-
dc.contributor.authorKok, KH-
dc.contributor.authorLau, SKP-
dc.contributor.authorWoo, PCY-
dc.contributor.authorLo, JYC-
dc.contributor.authorJin, D-
dc.contributor.authorShih, SR-
dc.contributor.authorYuen, KY-
dc.date.accessioned2019-08-18T15:04:30Z-
dc.date.available2019-08-18T15:04:30Z-
dc.date.issued2018-
dc.identifier.citationJournal of Clinical Investigation, 2018, v. 128 n. 11, p. 5163-5177-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/274575-
dc.description.abstractEnterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ–inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-γ–treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-γ for EV-A71 infection. Given that we detected high levels of IFN-γ in patients with severe EV-A71 infection, our findings extend the knowledge of the pathogenicity of EV-A71 in relation to entry factor expression upon IFN-γ stimulation and the therapeutic options for treating severe EV-A71–associated complications.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org-
dc.relation.ispartofJournal of Clinical Investigation-
dc.titleHuman tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus-
dc.typeArticle-
dc.identifier.emailYeung, ML: pmlyeung@hku.hk-
dc.identifier.emailYip, CY: yipcyril@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailTeng, LL: llteng@hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailCai, J: caijuice@hku.hk-
dc.identifier.emailZhang, J: zhangajx@hkucc.hku.hk-
dc.identifier.emailWong, LWM: louisewong@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailLau, SKP: skplau@hkucc.hku.hk-
dc.identifier.emailWoo, PCY: pcywoo@hkucc.hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityYeung, ML=rp01402-
dc.identifier.authorityYip, CY=rp01721-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityTeng, LL=rp00277-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityZhang, J=rp00413-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityLau, SKP=rp00486-
dc.identifier.authorityWoo, PCY=rp00430-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI99411-
dc.identifier.pmid30153112-
dc.identifier.scopuseid_2-s2.0-85055802133-
dc.identifier.hkuros301251-
dc.identifier.volume128-
dc.identifier.issue11-
dc.identifier.spage5163-
dc.identifier.epage5177-
dc.identifier.isiWOS:000448967200038-
dc.publisher.placeUnited States-

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