Article: Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract

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TitleTropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract
AuthorsChan, MCW1
Chan, RWY1
Yu, WCL1
Ho, CCC1
Yuen, KM1
Fong, JHM1
Tang, LLS1
Lai, WW1
Lo, ACY1
Chui, WH1
Sihoe, ADL1
Kwong, DLW1
Wong, DSH1
Tsao, GSW1
Poon, LLM1
Guan, Y1
Nicholls, JM1
Peiris, JSM2
Issue Date2010
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
CitationAmerican Journal Of Pathology, 2010, v. 176 n. 4, p. 1828-1840 [How to Cite?]
DOI: http://dx.doi.org/10.2353/ajpath.2010.091087
AbstractThe novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33°C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy. Copyright © American Society for Investigative Pathology.
ISSN0002-9440
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
DOIhttp://dx.doi.org/10.2353/ajpath.2010.091087
ISI Accession Number IDWOS:000276471500029
Funding AgencyGrant Number
Research Fund for Control of Infectious Disease06060552
08070842
Research Fund for Control of Infectious Disease, Health, Welfare, and Food Bureau, Hong Kong SAR Government
General Research Fund (HKU)7612/08M
7610/09M
7530/06M
7735/07M
Research Grants Council, Hong Kong SAR Government200907176007
The University of Hong Kong
National Institutes of Health (NIAID)HHSN266200700005C
Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR GovernmentAoE/M-12/06
Funding Information:

Supported by Research Fund for Control of Infectious Disease grant (Ref: LAB-15, RFCID commissioned study on human swine influenza virus and RFCID grant, reference no: 06060552, 08070842) 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 and 7610/09M to M.C.W.C., HKU 7530/06M to L.L.M.P and HKU 7735/07M to J.M.N), Research Grants Council, Hong Kong SAR Government; Small project funding (reference no: 200907176007 to R.W.Y.C), The University of Hong Kong; National Institutes of Health (NIAID contract HHSN266200700005C) and AoE Funding (AoE/M-12/06) from the Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR Government.

PubMed Central IDPMC2843473
ReferencesReferences in Scopus
GrantsReplication and pathogenesis of avian influenza A (H5N1) viruses in polarized human bronchial and alveolar epithelium
Establishment of primary human conjunctival epithelial cell in vitro and conjunctiva ex vivo organ culture model to study human infection of influenza virus.
Susceptibility of the upper respiratory tract to influenza virus infection following desialyation
Control of Pandemic and Inter-pandemic Influenza
DC Field
Value
dc.contributor.authorChan, MCW
dc.contributor.authorChan, RWY
dc.contributor.authorYu, WCL
dc.contributor.authorHo, CCC
dc.contributor.authorYuen, KM
dc.contributor.authorFong, JHM
dc.contributor.authorTang, LLS
dc.contributor.authorLai, WW
dc.contributor.authorLo, ACY
dc.contributor.authorChui, WH
dc.contributor.authorSihoe, ADL
dc.contributor.authorKwong, DLW
dc.contributor.authorWong, DSH
dc.contributor.authorTsao, GSW
dc.contributor.authorPoon, LLM
dc.contributor.authorGuan, Y
dc.contributor.authorNicholls, JM
dc.contributor.authorPeiris, JSM
dc.date.accessioned2011-09-23T05:42:39Z
dc.date.available2011-09-23T05:42:39Z
dc.date.issued2010
dc.description.abstractThe novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33°C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy. Copyright © American Society for Investigative Pathology.
dc.description.grantReplication and pathogenesis of avian influenza A (H5N1) viruses in polarized human bronchial and alveolar epithelium
dc.description.grantEstablishment of primary human conjunctival epithelial cell in vitro and conjunctiva ex vivo organ culture model to study human infection of influenza virus.
dc.description.grantSusceptibility of the upper respiratory tract to influenza virus infection following desialyation
dc.description.grantControl of Pandemic and Inter-pandemic Influenza
dc.description.grantcode96215
dc.description.grantcode101394
dc.description.grantcode99436
dc.description.grantcode97655
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationAmerican Journal Of Pathology, 2010, v. 176 n. 4, p. 1828-1840 [How to Cite?]
DOI: http://dx.doi.org/10.2353/ajpath.2010.091087
dc.identifier.doihttp://dx.doi.org/10.2353/ajpath.2010.091087
dc.identifier.epage1840
dc.identifier.hkuros172048
dc.identifier.isiWOS:000276471500029
Funding AgencyGrant Number
Research Fund for Control of Infectious Disease06060552
08070842
Research Fund for Control of Infectious Disease, Health, Welfare, and Food Bureau, Hong Kong SAR Government
General Research Fund (HKU)7612/08M
7610/09M
7530/06M
7735/07M
Research Grants Council, Hong Kong SAR Government200907176007
The University of Hong Kong
National Institutes of Health (NIAID)HHSN266200700005C
Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR GovernmentAoE/M-12/06
Funding Information:

Supported by Research Fund for Control of Infectious Disease grant (Ref: LAB-15, RFCID commissioned study on human swine influenza virus and RFCID grant, reference no: 06060552, 08070842) 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 and 7610/09M to M.C.W.C., HKU 7530/06M to L.L.M.P and HKU 7735/07M to J.M.N), Research Grants Council, Hong Kong SAR Government; Small project funding (reference no: 200907176007 to R.W.Y.C), The University of Hong Kong; National Institutes of Health (NIAID contract HHSN266200700005C) and AoE Funding (AoE/M-12/06) from the Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR Government.

dc.identifier.issn0002-9440
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmcidPMC2843473
dc.identifier.pmid20110407
dc.identifier.scopuseid_2-s2.0-77950584589
dc.identifier.spage1828
dc.identifier.urihttp://hdl.handle.net/10722/138946
dc.identifier.volume176
dc.languageeng
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
dc.publisher.placeUnited States
dc.relation.ispartofAmerican Journal of Pathology
dc.relation.referencesReferences in Scopus
dc.subject.meshBronchi - cytology
dc.subject.meshConjunctiva - virology
dc.subject.meshInfluenza A Virus, H1N1 Subtype - metabolism
dc.subject.meshInfluenza, Human - virology
dc.subject.meshRespiratory System - virology
dc.titleTropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. HKU-Pasteur Research Centre