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Article: Amino acid residues in the fusion peptide pocket regulate the ph of activation of the H5N1 influenza virus hemagglutinin protein

TitleAmino acid residues in the fusion peptide pocket regulate the ph of activation of the H5N1 influenza virus hemagglutinin protein
Authors
Issue Date2009
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2009, v. 83 n. 8, p. 3568-3580 How to Cite?
AbstractThe receptor specificity and cleavability of the hemagglutinin (HA) protein have been shown to regulate influenza A virus transmissibility and pathogenicity, but little is known about how its pH of activation contributes to these important biological properties. To identify amino acid residues that regulate the acid stability of the HA protein of H5N1 influenza viruses, we performed a mutational analysis of the HA protein of the moderately pathogenic A/chicken/Vietnam/C58/04 (H5N1) virus. Nineteen HA proteins containing point mutations in the HA2 coiled-coil domain or in an HA1 histidine or basic patch were generated. Wild-type and mutant HA plasmids were transiently transfected in cell culture and analyzed for total protein expression, surface expression, cleavage efficiency, pH of fusion, and pH of conformational change. Four mutations to residues in the fusion peptide pocket, Y23H and H24Q in the HA1 subunit and E105K and N114K in the HA2 subunit, and a K58I mutation in the HA2 coiled-coil domain significantly altered the pH of activation of the H5 HA protein. In some cases, the magnitude and direction of changes of individual mutations in the H5 HA protein differed considerably from similar mutations in other influenza A virus HA subtypes. Introduction of Y23H, H24Q, K58I, and N114K mutations into recombinant viruses resulted in virus-expressed HA proteins with similar shifts in the pH of fusion. Overall, the data show that residues comprising the fusion peptide pocket are important in triggering pH-dependent activation of the H5 HA protein. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179819
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.authorYen, HLen_US
dc.contributor.authorDubois, RMen_US
dc.contributor.authorBridges, OAen_US
dc.contributor.authorSalomon, Ren_US
dc.contributor.authorWebster, RGen_US
dc.contributor.authorRussell, CJen_US
dc.date.accessioned2012-12-19T10:05:11Z-
dc.date.available2012-12-19T10:05:11Z-
dc.date.issued2009en_US
dc.identifier.citationJournal Of Virology, 2009, v. 83 n. 8, p. 3568-3580en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/179819-
dc.description.abstractThe receptor specificity and cleavability of the hemagglutinin (HA) protein have been shown to regulate influenza A virus transmissibility and pathogenicity, but little is known about how its pH of activation contributes to these important biological properties. To identify amino acid residues that regulate the acid stability of the HA protein of H5N1 influenza viruses, we performed a mutational analysis of the HA protein of the moderately pathogenic A/chicken/Vietnam/C58/04 (H5N1) virus. Nineteen HA proteins containing point mutations in the HA2 coiled-coil domain or in an HA1 histidine or basic patch were generated. Wild-type and mutant HA plasmids were transiently transfected in cell culture and analyzed for total protein expression, surface expression, cleavage efficiency, pH of fusion, and pH of conformational change. Four mutations to residues in the fusion peptide pocket, Y23H and H24Q in the HA1 subunit and E105K and N114K in the HA2 subunit, and a K58I mutation in the HA2 coiled-coil domain significantly altered the pH of activation of the H5 HA protein. In some cases, the magnitude and direction of changes of individual mutations in the H5 HA protein differed considerably from similar mutations in other influenza A virus HA subtypes. Introduction of Y23H, H24Q, K58I, and N114K mutations into recombinant viruses resulted in virus-expressed HA proteins with similar shifts in the pH of fusion. Overall, the data show that residues comprising the fusion peptide pocket are important in triggering pH-dependent activation of the H5 HA protein. Copyright © 2009, 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.meshAmino Acid Substitution - Geneticsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCercopithecus Aethiopsen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshDna Mutational Analysisen_US
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - Genetics - Metabolismen_US
dc.subject.meshHydrogen-Ion Concentrationen_US
dc.subject.meshInfluenza A Virus, H5n1 Subtype - Physiologyen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshMutation, Missenseen_US
dc.subject.meshPoint Mutationen_US
dc.subject.meshProtein Structure, Tertiaryen_US
dc.subject.meshTransfectionen_US
dc.subject.meshVirus Internalizationen_US
dc.titleAmino acid residues in the fusion peptide pocket regulate the ph of activation of the H5N1 influenza virus hemagglutinin proteinen_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.02238-08en_US
dc.identifier.pmid19193808-
dc.identifier.scopuseid_2-s2.0-64049092310en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-64049092310&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume83en_US
dc.identifier.issue8en_US
dc.identifier.spage3568en_US
dc.identifier.epage3580en_US
dc.identifier.isiWOS:000264327300015-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridReed, ML=14012652700en_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridDuBois, RM=26430550700en_US
dc.identifier.scopusauthoridBridges, OA=35291358000en_US
dc.identifier.scopusauthoridSalomon, R=12786463900en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.identifier.scopusauthoridRussell, CJ=7401530472en_US
dc.identifier.citeulike4024046-

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