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Article: Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation

TitleInfluenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation
Authors
KeywordsSciences: comprehensive works
Medical sciences
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 1 How to Cite?
AbstractInfluenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE) cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004) and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998), the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of a2-6-linked sialic acid receptors and human airway trypsin-like (HAT) protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the epithelium regeneration, the data generated from the undifferentiated NHBE cultures may also be relevant to disease pathogenesis. © 2010 Chan et al.
Persistent Identifierhttp://hdl.handle.net/10722/57599
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Fund for Control of Infectious Disease
Hong Kong SAR Government
General Research FundHKU 7612/08M
Research Grants Council, Hong Kong SAR Government
AoE FundingAoE/M-12/06
University Grants Committee
Funding Information:

Funding: This work was supported by Research Fund for Control of Infectious Disease Grant (RFCID grants, reference no: 03040712 and 06060552) from the Research Fund for Control of Infectious Disease, Health, Welfare and Food Bureau, Hong Kong SAR Government and the General Research Fund (HKU 7612/08M), Research Grants Council, Hong Kong SAR Government (to M. C. W. C); and AoE Funding (AoE/M-12/06) from the Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, RWYen_HK
dc.contributor.authorYuen, KMen_HK
dc.contributor.authorYu, WCLen_HK
dc.contributor.authorHo, CCCen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorMalik Peiris, JSen_HK
dc.contributor.authorChan, MCWen_HK
dc.date.accessioned2010-04-21T04:46:17Z-
dc.date.available2010-04-21T04:46:17Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos One, 2010, v. 5 n. 1en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57599-
dc.description.abstractInfluenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE) cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004) and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998), the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of a2-6-linked sialic acid receptors and human airway trypsin-like (HAT) protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the epithelium regeneration, the data generated from the undifferentiated NHBE cultures may also be relevant to disease pathogenesis. © 2010 Chan et al.en_HK
dc.language.isoengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsPLoS ONE. Copyright © Public Library of Science.en_HK
dc.subjectSciences: comprehensive worksen_HK
dc.subjectMedical sciencesen_HK
dc.titleInfluenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiationen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, RWY: reneewy@hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailMalik Peiris, JS: malik@hkucc.hku.hken_HK
dc.identifier.emailChan, MCW: mchan@hku.hken_HK
dc.identifier.authorityChan, RWY=rp01596en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityMalik Peiris, JS=rp00410en_HK
dc.identifier.authorityChan, MCW=rp00420en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1371/journal.pone.0008713en_HK
dc.identifier.pmid20090947-
dc.identifier.pmcidPMC2806912en_HK
dc.identifier.scopuseid_2-s2.0-77649299022en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77649299022&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue1en_HK
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000273714900002-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridChan, RWY=26661379100en_HK
dc.identifier.scopusauthoridYuen, KM=35301205900en_HK
dc.identifier.scopusauthoridYu, WCL=26324133100en_HK
dc.identifier.scopusauthoridHo, CCC=35299371300en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridMalik Peiris, JS=7005486823en_HK
dc.identifier.scopusauthoridChan, MCW=26654715500en_HK

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