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Article: Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

TitleInfluenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells
Authors
Issue Date2009
PublisherBioMed Central Ltd. The Journal's web site is located at http://respiratory-research.com/
Citation
Respiratory Research, 2009, v. 10 n. 1, article no. 102 How to Cite?
AbstractBackground: Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.Aim: To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.Methods: We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.Results: We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.Conclusion: The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease. © 2009 Chan et al; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/57596
ISSN
2010 Impact Factor: 2.859
2015 SCImago Journal Rankings: 1.601
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Fund for Control of Infectious Disease, Health, Welfare and Food Bureau, Hong Kong SAR Government03040712
06060552
General Research FundHKU 761009M
Research Grants Council, Hong Kong SAR Government
Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR GovernmentAoE/M-12/06
Funding Information:

We are grateful for the help of Joanne HM Fong, Lynsia LS Tang and Thomas YO Chan with the cell culture, and molecular biology analysis, Mr. Kevin Fung for the immunohistochemistry. This work was supported by Research Fund for Control of Infectious Disease Grant (RFCID grant, 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 761009M), 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.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, MCWen_HK
dc.contributor.authorChan, RWYen_HK
dc.contributor.authorYu, WCLen_HK
dc.contributor.authorHo, CCCen_HK
dc.contributor.authorChui, WHen_HK
dc.contributor.authorLo, CKen_HK
dc.contributor.authorYuen, KMen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorPeiris, JMen_HK
dc.date.accessioned2010-04-20T03:25:18Z-
dc.date.available2010-04-20T03:25:18Z-
dc.date.issued2009en_HK
dc.identifier.citationRespiratory Research, 2009, v. 10 n. 1, article no. 102en_HK
dc.identifier.issn1465-9921en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57596-
dc.description.abstractBackground: Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.Aim: To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.Methods: We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.Results: We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.Conclusion: The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease. © 2009 Chan et al; licensee BioMed Central Ltd.en_HK
dc.language.isoengen_HK
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://respiratory-research.com/en_HK
dc.relation.ispartofRespiratory Researchen_HK
dc.rightsRespiratory Research. Copyright © BioMed Central Ltd.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCell Polarityen_HK
dc.subject.meshEndothelial Cells - immunology - virologyen_HK
dc.subject.meshEpithelial Cells - immunology - virologyen_HK
dc.subject.meshImmunity, Innateen_Hk
dc.subject.meshInfluenza A Virus, H1N1 Subtype - immunology - pathogenicityend_HK
dc.titleInfluenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, MCW: mchan@hku.hken_HK
dc.identifier.emailChan, RWY: reneewy@hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JM: malik@hkucc.hku.hken_HK
dc.identifier.authorityChan, MCW=rp00420en_HK
dc.identifier.authorityChan, RWY=rp01596en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityPeiris, JM=rp00410en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1186/1465-9921-10-102en_HK
dc.identifier.pmid19874627en_HK
dc.identifier.pmcidPMC2780994en_HK
dc.identifier.scopuseid_2-s2.0-73949106803en_HK
dc.identifier.hkuros167950-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73949106803&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue1-
dc.identifier.spagearticle no. 102-
dc.identifier.epagearticle no. 102-
dc.identifier.isiWOS:000272291600001-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectInfluenza A (H5N1) virus infection in human primary type I and type II alveolar epithelial cells: Cell tropism, inflammatory responses and apoptosis-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.relation.projectPrimary human lung epithelial cells as an in-vitro model to study the pathogenesis of SARS coronavirus infection-
dc.relation.projectReplication and pathogenesis of avian influenza A (H5N1) viruses in polarized human bronchial and alveolar epithelium-
dc.identifier.scopusauthoridChan, MCW=26654715500en_HK
dc.identifier.scopusauthoridChan, RWY=26661379100en_HK
dc.identifier.scopusauthoridYu, WCL=26324133100en_HK
dc.identifier.scopusauthoridHo, CCC=35299371300en_HK
dc.identifier.scopusauthoridChui, WH=7003524497en_HK
dc.identifier.scopusauthoridLo, CK=16162440300en_HK
dc.identifier.scopusauthoridYuen, KM=35301205900en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridPeiris, JM=7005486823en_HK
dc.identifier.citeulike6059678-

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