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Article: Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.

TitleSystems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2009, v. 4 n. 12, p. e8072 How to Cite?
AbstractHuman disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-alpha genes. A network-based analysis suggests that the synergy between IFN-beta and TNF-alpha results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease.
Persistent Identifierhttp://hdl.handle.net/10722/141721
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIAIDHHSN26620070005C
Council of the Hong Kong Special Administrative RegionHKU1/05C
Area of Excellence Scheme of the University Grants CommitteeAoE/M-12/06
Funding Information:

This work was supported by the National Institutes of Health Grant (NIAID Contract: HHSN26620070005C; http://www.niaid.nih.gov/ncn/grants/default_grants.htm), the Canadian Institutes of Health Research Grant (grant number: TPA-90195; http://www.cihr.ca/e/193.html) and grants from the Research Grants Council of the Hong Kong Special Administrative Region, the Central Allocation Grant (grant number: HKU1/05C; http://www.ugc.edu.hk/eng/rgc/crf/crf.htm) and Area of Excellence Scheme of the University Grants Committee (grant number: AoE/M-12/06; http://www.ugc.edu.hk/eng/ugc/activity/aoes/aoes.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References
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DC FieldValueLanguage
dc.contributor.authorLee, SMen_HK
dc.contributor.authorGardy, JLen_HK
dc.contributor.authorCheung, CYen_HK
dc.contributor.authorCheung, TKen_HK
dc.contributor.authorHui, KPen_HK
dc.contributor.authorIp, NYen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorHancock, REen_HK
dc.contributor.authorPeiris, JSen_HK
dc.date.accessioned2011-09-27T02:59:13Z-
dc.date.available2011-09-27T02:59:13Z-
dc.date.issued2009en_HK
dc.identifier.citationPlos One, 2009, v. 4 n. 12, p. e8072en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141721-
dc.description.abstractHuman disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-alpha genes. A network-based analysis suggests that the synergy between IFN-beta and TNF-alpha results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease.en_HK
dc.languageengen_US
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.subject.meshHost-Pathogen Interactions - genetics - immunology-
dc.subject.meshInfluenza A Virus, H1N1 Subtype - immunology-
dc.subject.meshInfluenza A Virus, H5N1 Subtype - immunology-
dc.subject.meshInfluenza in Birds - immunology - virology-
dc.subject.meshInfluenza, Human - immunology - virology-
dc.titleSystems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.en_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SM: suki@hku.hken_HK
dc.identifier.emailCheung, CY: chungey@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JS: malik@hkucc.hku.hken_HK
dc.identifier.authorityLee, SM=rp01536en_HK
dc.identifier.authorityCheung, CY=rp00404en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, JS=rp00410en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0008072en_HK
dc.identifier.pmid20011590-
dc.identifier.pmcidPMC2788213-
dc.identifier.scopuseid_2-s2.0-77954074054en_HK
dc.identifier.hkuros171560-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954074054&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume4en_HK
dc.identifier.issue12en_HK
dc.identifier.spagee8072en_HK
dc.identifier.epagee8072en_HK
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000272830300001-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridLee, SM=35435155600en_HK
dc.identifier.scopusauthoridGardy, JL=7801475389en_HK
dc.identifier.scopusauthoridCheung, CY=7202061836en_HK
dc.identifier.scopusauthoridCheung, TK=16229531100en_HK
dc.identifier.scopusauthoridHui, KP=24492032000en_HK
dc.identifier.scopusauthoridIp, NY=7005756760en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridHancock, RE=7201916259en_HK
dc.identifier.scopusauthoridPeiris, JS=7005486823en_HK
dc.identifier.citeulike10442645-

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