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Article: The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04

TitleThe polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04
Authors
Issue Date2006
PublisherRockefeller University Press. The Journal's web site is located at http://www.jem.org
Citation
Journal Of Experimental Medicine, 2006, v. 203 n. 3, p. 689-697 How to Cite?
AbstractH5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified to elucidate and target virulence factors. We applied reverse genetics to generate H5N1 reassortants combining genes of lethal A/Vietnam/1203/04 (VN1203), a fatal human case isolate, and nonlethal A/chicken/Vietnam/C58/04 (CH58) and tested their pathogenicity in ferrets and mice. The viruses' hemagglutinins have six amino acids differences, identical cleavage sites, and avian-like α-(2,3)-linked receptor specificity. Surprisingly, exchanging hemagglutinin and neuraminidase genes did not alter pathogenicity, but substituting CH58 polymerase genes completely attenuated VN1203 virulence and reduced viral polymerase activity. CH58's NS gene partially attenuated VN1203 in ferrets but not in mice. Our findings suggest that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier. Thus, novel antivirals targeting polymerase proteins should be developed. JEM © The Rockefeller University Press.
Persistent Identifierhttp://hdl.handle.net/10722/179788
ISSN
2015 Impact Factor: 11.24
2015 SCImago Journal Rankings: 10.762
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSalomon, Ren_US
dc.contributor.authorFranks, Jen_US
dc.contributor.authorGovorkova, EAen_US
dc.contributor.authorIlyushina, NAen_US
dc.contributor.authorYen, HLen_US
dc.contributor.authorHulsePost, DJen_US
dc.contributor.authorHumberd, Jen_US
dc.contributor.authorTrichet, Men_US
dc.contributor.authorRehg, JEen_US
dc.contributor.authorWebby, RJen_US
dc.contributor.authorWebster, RGen_US
dc.contributor.authorHoffmann, Een_US
dc.date.accessioned2012-12-19T10:04:43Z-
dc.date.available2012-12-19T10:04:43Z-
dc.date.issued2006en_US
dc.identifier.citationJournal Of Experimental Medicine, 2006, v. 203 n. 3, p. 689-697en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttp://hdl.handle.net/10722/179788-
dc.description.abstractH5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified to elucidate and target virulence factors. We applied reverse genetics to generate H5N1 reassortants combining genes of lethal A/Vietnam/1203/04 (VN1203), a fatal human case isolate, and nonlethal A/chicken/Vietnam/C58/04 (CH58) and tested their pathogenicity in ferrets and mice. The viruses' hemagglutinins have six amino acids differences, identical cleavage sites, and avian-like α-(2,3)-linked receptor specificity. Surprisingly, exchanging hemagglutinin and neuraminidase genes did not alter pathogenicity, but substituting CH58 polymerase genes completely attenuated VN1203 virulence and reduced viral polymerase activity. CH58's NS gene partially attenuated VN1203 in ferrets but not in mice. Our findings suggest that for high virulence in mammalian species an avian H5N1 virus with a cleavable hemagglutinin requires adaptive changes in polymerase genes to overcome the species barrier. Thus, novel antivirals targeting polymerase proteins should be developed. JEM © The Rockefeller University Press.en_US
dc.languageengen_US
dc.publisherRockefeller University Press. The Journal's web site is located at http://www.jem.orgen_US
dc.relation.ispartofJournal of Experimental Medicineen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntiviral Agents - Therapeutic Useen_US
dc.subject.meshChickens - Virologyen_US
dc.subject.meshEnzyme Inhibitors - Therapeutic Useen_US
dc.subject.meshFerrets - Virologyen_US
dc.subject.meshGenetic Variationen_US
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshInfluenza A Virus, H5n1 Subtype - Genetics - Pathogenicityen_US
dc.subject.meshInfluenza In Birds - Drug Therapy - Genetics - Pathologyen_US
dc.subject.meshInfluenza, Human - Drug Therapy - Genetics - Pathologyen_US
dc.subject.meshMiceen_US
dc.subject.meshNeuraminidase - Geneticsen_US
dc.subject.meshProtein Processing, Post-Translational - Geneticsen_US
dc.subject.meshRna Replicase - Antagonists & Inhibitors - Geneticsen_US
dc.subject.meshSpecies Specificityen_US
dc.subject.meshVirulence Factors - Geneticsen_US
dc.titleThe polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04en_US
dc.typeArticleen_US
dc.identifier.emailYen, HL: hyen@hku.hken_US
dc.identifier.authorityYen, HL=rp00304en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1084/jem.20051938en_US
dc.identifier.pmid16533883-
dc.identifier.scopuseid_2-s2.0-33645058912en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645058912&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume203en_US
dc.identifier.issue3en_US
dc.identifier.spage689en_US
dc.identifier.epage697en_US
dc.identifier.isiWOS:000236520800022-
dc.publisher.placeUnited Statesen_US
dc.identifier.f100011602-
dc.identifier.scopusauthoridSalomon, R=12786463900en_US
dc.identifier.scopusauthoridFranks, J=12786180500en_US
dc.identifier.scopusauthoridGovorkova, EA=7003837718en_US
dc.identifier.scopusauthoridIlyushina, NA=6506741015en_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridHulsePost, DJ=11940084300en_US
dc.identifier.scopusauthoridHumberd, J=6506769380en_US
dc.identifier.scopusauthoridTrichet, M=12787608800en_US
dc.identifier.scopusauthoridRehg, JE=7004835777en_US
dc.identifier.scopusauthoridWebby, RJ=35448064800en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.identifier.scopusauthoridHoffmann, E=7201369718en_US
dc.identifier.citeulike4544876-

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