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Article: Viral genetic determinants of h5n1 influenza viruses that contribute to cytokine dysregulation

TitleViral genetic determinants of h5n1 influenza viruses that contribute to cytokine dysregulation
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org
Citation
Journal Of Infectious Diseases, 2009, v. 200 n. 7, p. 1104-1112 How to Cite?
AbstractHuman disease caused by highly pathogenic avian influenza (H5N1) is associated with fulminant viral pneumonia and mortality rates in excess of 60%. Cytokine dysregulation is thought to contribute to its pathogenesis. In comparison with human seasonal influenza (H1N1) viruses, clade 1, 2.1, and 2.2 H5N1 viruses induced higher levels of tumor necrosis factor-α in primary human macrophages. To understand viral genetic determinants responsible for this hyperinduction of cytokines, we constructed recombinant viruses containing different combinations of genes from high-cytokine (A/Vietnam/1203/04) and low-cytokine (A/WSN/33) phenotype HlNl viruses and tested their cytokine-inducing phenotype in human macrophages. Our results suggest that the H5N1 polymerase gene segments, and to a lesser extent the NS gene segment, contribute to cytokine hyperinduction in human macrophages and that a putative H5 pandemic virus that may arise through genetic reassortment between H5N1 and one of the current seasonal influenza viruses may have a markedly altered cytokine phenotype. © 2009 by the Infectious Diseases Society of America. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/78991
ISSN
2015 Impact Factor: 6.344
2015 SCImago Journal Rankings: 4.000
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthHHSN266200700005C
Research Grants Council of Hong Kong1/05C
University Grants Committee of the Hong Kong Special Administrative Region, ChinaAoE/M-12/06
Research Fund for the Control of Infectious Diseases01030172
Funding Information:

Financial support: National Institutes of Health (National Institute of Allergy and Infectious Diseases contract HHSN266200700005C), Research Grants Council of Hong Kong (Central Allocation grant HKU 1/05C), University Grants Committee of the Hong Kong Special Administrative Region, China (Area of Excellence grant; project AoE/M-12/06), and Research Fund for the Control of Infectious Diseases (grant 01030172).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorMok, KPen_HK
dc.contributor.authorWong, CHKen_HK
dc.contributor.authorCheung, CYen_HK
dc.contributor.authorChan, MCen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.date.accessioned2010-09-06T07:49:16Z-
dc.date.available2010-09-06T07:49:16Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Infectious Diseases, 2009, v. 200 n. 7, p. 1104-1112en_HK
dc.identifier.issn0022-1899en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78991-
dc.description.abstractHuman disease caused by highly pathogenic avian influenza (H5N1) is associated with fulminant viral pneumonia and mortality rates in excess of 60%. Cytokine dysregulation is thought to contribute to its pathogenesis. In comparison with human seasonal influenza (H1N1) viruses, clade 1, 2.1, and 2.2 H5N1 viruses induced higher levels of tumor necrosis factor-α in primary human macrophages. To understand viral genetic determinants responsible for this hyperinduction of cytokines, we constructed recombinant viruses containing different combinations of genes from high-cytokine (A/Vietnam/1203/04) and low-cytokine (A/WSN/33) phenotype HlNl viruses and tested their cytokine-inducing phenotype in human macrophages. Our results suggest that the H5N1 polymerase gene segments, and to a lesser extent the NS gene segment, contribute to cytokine hyperinduction in human macrophages and that a putative H5 pandemic virus that may arise through genetic reassortment between H5N1 and one of the current seasonal influenza viruses may have a markedly altered cytokine phenotype. © 2009 by the Infectious Diseases Society of America. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org en_HK
dc.relation.ispartofJournal of Infectious Diseasesen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCytokines - metabolism-
dc.subject.meshDNA-Directed DNA Polymerase - genetics - metabolism-
dc.subject.meshGene Expression Regulation, Viral - physiology-
dc.subject.meshHemagglutinins - genetics - metabolism-
dc.subject.meshInfluenza A Virus, H5N1 Subtype - classification - genetics-
dc.titleViral genetic determinants of h5n1 influenza viruses that contribute to cytokine dysregulationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1899&volume=200&issue=7&spage=1104&epage=1112&date=2009&atitle=Viral+Genetic+Determinants+of+H5N1+Influenza+Viruses+That+Contribute+to+Cytokine+Dysregulationen_HK
dc.identifier.emailMok, KP: ch02mkp@hkucc.hku.hken_HK
dc.identifier.emailCheung, CY: chungey@hkucc.hku.hken_HK
dc.identifier.emailChan, MC: mchan@hkucc.hku.hken_HK
dc.identifier.emailLee, SMY: suki@hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.authorityMok, KP=rp01805en_HK
dc.identifier.authorityCheung, CY=rp00404en_HK
dc.identifier.authorityChan, MC=rp00420en_HK
dc.identifier.authorityLee, SMY=rp01536en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1086/605606en_HK
dc.identifier.pmid19694514-
dc.identifier.scopuseid_2-s2.0-70349320383en_HK
dc.identifier.hkuros167844en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349320383&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume200en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1104en_HK
dc.identifier.epage1112en_HK
dc.identifier.eissn0022-1899-
dc.identifier.isiWOS:000269475000013-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectThe role of influenza virus gene constellation and viral morphology on cytokine induction, pathogenesis and viral virulence-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridMok, KP=35170851200en_HK
dc.identifier.scopusauthoridWong, CHK=11039790300en_HK
dc.identifier.scopusauthoridCheung, CY=7202061836en_HK
dc.identifier.scopusauthoridChan, MC=26654715500en_HK
dc.identifier.scopusauthoridLee, SMY=35435155600en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.citeulike5496938-

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