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Article: Identification and characterization of GLDC as host susceptibility gene to severe influenza

TitleIdentification and characterization of GLDC as host susceptibility gene to severe influenza
Authors
Keywordsanimal experiment
animal model
Bagg albino mouse
clinical outcome
controlled study
Issue Date2019
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1757-4684
Citation
EMBO Molecular Medicine, 2019, v. 11 n. 1, p. article no. e9528 How to Cite?
AbstractGlycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.
Persistent Identifierhttp://hdl.handle.net/10722/272055
ISSN
2017 Impact Factor: 10.293
2015 SCImago Journal Rankings: 5.546
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, J-
dc.contributor.authorWANG, D-
dc.contributor.authorWONG, BHY-
dc.contributor.authorLi, C-
dc.contributor.authorPoon, VKM-
dc.contributor.authorWen, L-
dc.contributor.authorZhao, X-
dc.contributor.authorChiu, MC-
dc.contributor.authorLiu, X-
dc.contributor.authorYe, Z-
dc.contributor.authorYuan, S-
dc.contributor.authorSze, KH-
dc.contributor.authorChan, JFW-
dc.contributor.authorChu, H-
dc.contributor.authorTo, KKW-
dc.contributor.authorYuen, KY-
dc.date.accessioned2019-07-20T10:34:46Z-
dc.date.available2019-07-20T10:34:46Z-
dc.date.issued2019-
dc.identifier.citationEMBO Molecular Medicine, 2019, v. 11 n. 1, p. article no. e9528-
dc.identifier.issn1757-4676-
dc.identifier.urihttp://hdl.handle.net/10722/272055-
dc.description.abstractGlycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFNβ‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significantly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1757-4684-
dc.relation.ispartofEMBO Molecular Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectBagg albino mouse-
dc.subjectclinical outcome-
dc.subjectcontrolled study-
dc.titleIdentification and characterization of GLDC as host susceptibility gene to severe influenza-
dc.typeArticle-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.15252/emmm.201809528-
dc.identifier.pmid30498026-
dc.identifier.pmcidPMC6328914-
dc.identifier.scopuseid_2-s2.0-85057524260-
dc.identifier.hkuros298877-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spagearticle no. e9528-
dc.identifier.epagearticle no. e9528-
dc.publisher.placeGermany-

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