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Article: The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity and transmissibility in ducks

TitleThe pH of activation of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity and transmissibility in ducks
Authors
Issue Date2010
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2010, v. 84 n. 3, p. 1527-1535 How to Cite?
AbstractWhile the molecular mechanism of membrane fusion by the influenza virus hemagglutinin (HA) protein has been studied extensively in vitro, the role of acid-dependent HA protein activation in virus replication, pathogenesis, and transmission in vivo has not been characterized. To investigate the biological significance of the pH of activation of the HA protein, we compared the properties of four recombinant viruses with altered HA protein acid stability to those of wild-type influenza virus A/chicken/Vietnam/C58/04 (H5N1) in vitro and in mallards. Membrane fusion by wild-type virus was activated at pH 5.9. Wild-type virus had a calculated environmental persistence of 62 days and caused extensive morbidity, mortality, shedding, and transmission in mallards. An N114K mutation that increased the pH of HA activation by 0.5 unit resulted in decreased replication, genetic stability, and environmental stability. Changes of +0.4 and +0.5 unit in the pH of activation by Y23H and K58I mutations, respectively, reduced weight loss, mortality, shedding, and transmission in mallards. An H24Q mutation that decreased the pH of activation by 0.3 unit resulted in weight loss, mortality, clinical symptoms, and shedding similar to those of the wild type. However, the HA-H241Q virus was shed more extensively into drinking water and persisted longer in the environment. The pH of activation of the H5 HA protein plays a key role in the propagation of H5N1 influenza viruses in ducks and may be a novel molecular factor in the ecology of influenza viruses. The data also demonstrate that H5N1 neuraminidase activity increases the pH of activation of the HA protein in vitro. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179824
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorReed, MLen_US
dc.contributor.authorBridges, OAen_US
dc.contributor.authorSeiler, Pen_US
dc.contributor.authorKim, JKen_US
dc.contributor.authorYen, HLen_US
dc.contributor.authorSalomon, Ren_US
dc.contributor.authorGovorkova, EAen_US
dc.contributor.authorWebster, RGen_US
dc.contributor.authorRussell, CJen_US
dc.date.accessioned2012-12-19T10:05:14Z-
dc.date.available2012-12-19T10:05:14Z-
dc.date.issued2010en_US
dc.identifier.citationJournal Of Virology, 2010, v. 84 n. 3, p. 1527-1535en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/179824-
dc.description.abstractWhile the molecular mechanism of membrane fusion by the influenza virus hemagglutinin (HA) protein has been studied extensively in vitro, the role of acid-dependent HA protein activation in virus replication, pathogenesis, and transmission in vivo has not been characterized. To investigate the biological significance of the pH of activation of the HA protein, we compared the properties of four recombinant viruses with altered HA protein acid stability to those of wild-type influenza virus A/chicken/Vietnam/C58/04 (H5N1) in vitro and in mallards. Membrane fusion by wild-type virus was activated at pH 5.9. Wild-type virus had a calculated environmental persistence of 62 days and caused extensive morbidity, mortality, shedding, and transmission in mallards. An N114K mutation that increased the pH of HA activation by 0.5 unit resulted in decreased replication, genetic stability, and environmental stability. Changes of +0.4 and +0.5 unit in the pH of activation by Y23H and K58I mutations, respectively, reduced weight loss, mortality, shedding, and transmission in mallards. An H24Q mutation that decreased the pH of activation by 0.3 unit resulted in weight loss, mortality, clinical symptoms, and shedding similar to those of the wild type. However, the HA-H241Q virus was shed more extensively into drinking water and persisted longer in the environment. The pH of activation of the H5 HA protein plays a key role in the propagation of H5N1 influenza viruses in ducks and may be a novel molecular factor in the ecology of influenza viruses. The data also demonstrate that H5N1 neuraminidase activity increases the pH of activation of the HA protein in vitro. Copyright © 2010, American Society for Microbiology. All Rights Reserved.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBird Diseases - Transmissionen_US
dc.subject.meshDucksen_US
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - Genetics - Metabolismen_US
dc.subject.meshHydrogen-Ion Concentrationen_US
dc.subject.meshInfluenza A Virus, H5n1 Subtype - Genetics - Pathogenicityen_US
dc.subject.meshMembrane Fusionen_US
dc.subject.meshMutationen_US
dc.subject.meshRecombination, Geneticen_US
dc.titleThe pH of activation of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity and transmissibility in ducksen_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.doi10.1128/JVI.02069-09en_US
dc.identifier.pmid19923184-
dc.identifier.scopuseid_2-s2.0-73949160128en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73949160128&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume84en_US
dc.identifier.issue3en_US
dc.identifier.spage1527en_US
dc.identifier.epage1535en_US
dc.identifier.isiWOS:000273531600030-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridReed, ML=14012652700en_US
dc.identifier.scopusauthoridBridges, OA=35291358000en_US
dc.identifier.scopusauthoridSeiler, P=7005281020en_US
dc.identifier.scopusauthoridKim, JK=11139429600en_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridSalomon, R=12786463900en_US
dc.identifier.scopusauthoridGovorkova, EA=7003837718en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.identifier.scopusauthoridRussell, CJ=7401530472en_US

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