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Article: Host immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cells

TitleHost immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cells
Authors
KeywordsApoptosis
Avian influenza virus
Bronchial epithelial cells
Chemokines
Cytokines
H9N2
Host responses
Issue Date2010
PublisherAmerican Thoracic Society. The Journal's web site is located at http://ajrcmb.atsjournals.org
Citation
American Journal Of Respiratory Cell And Molecular Biology, 2010, v. 44 n. 1, p. 24-33 How to Cite?
AbstractThe avian influenza virus H9N2 subtype has circulated in wild birds, is prevalent in domestic poultry, and has successfully crossed the species boundary to infect humans. Phylogenetic analyses showed that viruses of this subtype appear to have contributed to the generation of highly pathogenic H5N1 viruses. Little is known about the host responses to H9N2 viruses in human airway respiratory epithelium, the primary portal for viral infection. Using an apically differentiated primary human tracheobronchial epithelial (TBE) culture, we examined host immune responses to infection by an avian H9N2 virus, in comparison with a human H9N2 isolate. We found that IFN-β was the prominent antiviral component, whereas interferon gamma-induced protein 10 kDa (IP-10), chemokine (C-C motif) ligand (CCL)-5 and TNF-α may be critical in proinflammatory responses to H9N2 viruses. In contrast, proinflammatory IL-1β, IL-8, and even IL-6 may only play a minor role in pathogenicity. Apparently Toll-like receptor (TLR)-3, TLR-7, and melanoma differentiation- associated gene 5 (MDA-5) contributed to the innate immunity against theH9N2viruses, andMDA-5was important in the induction of IFN-β. We showed that the avian H9N2 virus induced apoptosis through the mitochondria/cytochrome c-mediated intrinsic pathway, in addition to the caspase 8-mediated extrinsic pathway, as evidenced by the cytosolic presence of active caspase 9 and cytochrome c, independent of truncated BH3 interacting domain death agonist (Bid) activation. Further, we demonstrated that FLICE-like inhibitory protein (FLIP), an apoptotic dual regulator, and the p53- dependent Bcl-2 family members, Bax and Bcl-x s, appeared to be involved in the regulation of extrinsic and intrinsic apoptotic pathways, respectively. The findings in this study will further our understanding of host defense mechanisms and the pathogenesis of H9N2 influenza viruses in human respiratory epithelium.
Persistent Identifierhttp://hdl.handle.net/10722/125148
ISSN
2015 Impact Factor: 4.082
2015 SCImago Journal Rankings: 1.622
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthHL085311
Department of Homeland Security National Center for Foreign Animal and Zoonotic Disease Defense
National Natural Science Foundation of China30971450/C0703
State Key Laboratory of Pharmaceutical Biotechnology of Nanjing UniversityKFGW-200902
Funding Information:

R. H. received a sponsored grant (HL085311) from the National Institutes of Health for more than $ 100,001. None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorXing, Zen_HK
dc.contributor.authorHarper, Ren_HK
dc.contributor.authorAnunciacion, Jen_HK
dc.contributor.authorYang, Zen_HK
dc.contributor.authorGao, Wen_HK
dc.contributor.authorQu, Ben_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorCardona, CJen_HK
dc.date.accessioned2010-10-31T11:14:07Z-
dc.date.available2010-10-31T11:14:07Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Respiratory Cell And Molecular Biology, 2010, v. 44 n. 1, p. 24-33en_HK
dc.identifier.issn1044-1549en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125148-
dc.description.abstractThe avian influenza virus H9N2 subtype has circulated in wild birds, is prevalent in domestic poultry, and has successfully crossed the species boundary to infect humans. Phylogenetic analyses showed that viruses of this subtype appear to have contributed to the generation of highly pathogenic H5N1 viruses. Little is known about the host responses to H9N2 viruses in human airway respiratory epithelium, the primary portal for viral infection. Using an apically differentiated primary human tracheobronchial epithelial (TBE) culture, we examined host immune responses to infection by an avian H9N2 virus, in comparison with a human H9N2 isolate. We found that IFN-β was the prominent antiviral component, whereas interferon gamma-induced protein 10 kDa (IP-10), chemokine (C-C motif) ligand (CCL)-5 and TNF-α may be critical in proinflammatory responses to H9N2 viruses. In contrast, proinflammatory IL-1β, IL-8, and even IL-6 may only play a minor role in pathogenicity. Apparently Toll-like receptor (TLR)-3, TLR-7, and melanoma differentiation- associated gene 5 (MDA-5) contributed to the innate immunity against theH9N2viruses, andMDA-5was important in the induction of IFN-β. We showed that the avian H9N2 virus induced apoptosis through the mitochondria/cytochrome c-mediated intrinsic pathway, in addition to the caspase 8-mediated extrinsic pathway, as evidenced by the cytosolic presence of active caspase 9 and cytochrome c, independent of truncated BH3 interacting domain death agonist (Bid) activation. Further, we demonstrated that FLICE-like inhibitory protein (FLIP), an apoptotic dual regulator, and the p53- dependent Bcl-2 family members, Bax and Bcl-x s, appeared to be involved in the regulation of extrinsic and intrinsic apoptotic pathways, respectively. The findings in this study will further our understanding of host defense mechanisms and the pathogenesis of H9N2 influenza viruses in human respiratory epithelium.en_HK
dc.languageengen_HK
dc.publisherAmerican Thoracic Society. The Journal's web site is located at http://ajrcmb.atsjournals.orgen_HK
dc.relation.ispartofAmerican Journal of Respiratory Cell and Molecular Biologyen_HK
dc.subjectApoptosisen_HK
dc.subjectAvian influenza virusen_HK
dc.subjectBronchial epithelial cellsen_HK
dc.subjectChemokinesen_HK
dc.subjectCytokinesen_HK
dc.subjectH9N2en_HK
dc.subjectHost responsesen_HK
dc.subject.meshApoptosis - genetics-
dc.subject.meshBronchi - immunology - pathology - virology-
dc.subject.meshEpithelial Cells - immunology - pathology - virology-
dc.subject.meshImmunity, Innate - genetics-
dc.subject.meshInfluenza A Virus, H9N2 Subtype - growth and development - pathogenicity-
dc.titleHost immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1044-1549&volume=44&issue=1&spage=24&epage=33&date=2010&atitle=Host+immune+and+apoptotic+responses+to+avian+influenza+virus+H9N2+in+human+tracheobronchial+epithelial+cells-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1165/rcmb.2009-0120OCen_HK
dc.identifier.pmid20118223-
dc.identifier.pmcidPMC3159084-
dc.identifier.scopuseid_2-s2.0-77958156908en_HK
dc.identifier.hkuros180286en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77958156908&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume44en_HK
dc.identifier.issue1en_HK
dc.identifier.spage24en_HK
dc.identifier.epage33en_HK
dc.identifier.isiWOS:000289770600003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridXing, Z=7201601324en_HK
dc.identifier.scopusauthoridHarper, R=35512766500en_HK
dc.identifier.scopusauthoridAnunciacion, J=35408717700en_HK
dc.identifier.scopusauthoridYang, Z=26650248200en_HK
dc.identifier.scopusauthoridGao, W=37070623900en_HK
dc.identifier.scopusauthoridQu, B=36017564300en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridCardona, CJ=7004278576en_HK

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