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Article: Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread

TitleChanges in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread
Authors
Issue Date2009
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2009, v. 106 n. 1, p. 286-291 How to Cite?
AbstractThe HA of influenza virus is a receptor-binding and fusion protein that is required to initiate infection. The HA receptor-binding domain determines the species of sialyl receptors recognized by influenza viruses. Here, we demonstrate that changes in the HA receptor-binding domain alter the ability of the H5N1 virus to spread systemically in mice. The A/Vietnam/1203/04 (VN1203) and A/Hong Kong/213/03 (HK213) viruses are consistently lethal to domestic chickens but differ in their pathogenicity to mammals. Insertion of the VN1203 HA and neuraminidase (NA) genes into recombinant HK213 virus expanded its tissue tropism and increased its lethality in mice; conversely, insertion of HK213 HA and NA genes into recombinant VN1203 virus decreased its systemic spread and lethality. The VN1203 and HK213 HAs differ by 10 aa, and HK213 HA has shown greater binding affinity for synthetic α2,6-linked sialyl receptor. Introduction of an S227N change and removal of N-linked glycosylation at residue 158 increased the α2,6-binding affinity of VN1203 HA. Recombinant VN1203 virus carrying the S227N change alone or with the residue-158 glycosylation site removed showed reduced lethality and systemic spread in mice but not in domestic chickens. Wild-type VN1203 virus exhibited the greatest efficiency in systemic spread after intramuscular inoculation and in infection of mouse bone marrow-derived dendritic cells and conventional pulmonary dendritic cells. These results show that VN1203 HA glycoprotein confers pathogenicity by facilitating systemic spread in mice; they also suggest that a minor change in receptor binding domain may modulate the virulence of H5N1 viruses. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/179817
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYen, HLen_US
dc.contributor.authorAldridge, JRen_US
dc.contributor.authorBoon, ACMen_US
dc.contributor.authorIlyushina, NAen_US
dc.contributor.authorSalomon, Ren_US
dc.contributor.authorHulsePost, DJen_US
dc.contributor.authorMarjuki, Hen_US
dc.contributor.authorFranks, Jen_US
dc.contributor.authorBoltz, DAen_US
dc.contributor.authorBush, Den_US
dc.contributor.authorLipatov, ASen_US
dc.contributor.authorWebby, RJen_US
dc.contributor.authorRehg, JEen_US
dc.contributor.authorWebster, RGen_US
dc.date.accessioned2012-12-19T10:05:10Z-
dc.date.available2012-12-19T10:05:10Z-
dc.date.issued2009en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2009, v. 106 n. 1, p. 286-291en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/179817-
dc.description.abstractThe HA of influenza virus is a receptor-binding and fusion protein that is required to initiate infection. The HA receptor-binding domain determines the species of sialyl receptors recognized by influenza viruses. Here, we demonstrate that changes in the HA receptor-binding domain alter the ability of the H5N1 virus to spread systemically in mice. The A/Vietnam/1203/04 (VN1203) and A/Hong Kong/213/03 (HK213) viruses are consistently lethal to domestic chickens but differ in their pathogenicity to mammals. Insertion of the VN1203 HA and neuraminidase (NA) genes into recombinant HK213 virus expanded its tissue tropism and increased its lethality in mice; conversely, insertion of HK213 HA and NA genes into recombinant VN1203 virus decreased its systemic spread and lethality. The VN1203 and HK213 HAs differ by 10 aa, and HK213 HA has shown greater binding affinity for synthetic α2,6-linked sialyl receptor. Introduction of an S227N change and removal of N-linked glycosylation at residue 158 increased the α2,6-binding affinity of VN1203 HA. Recombinant VN1203 virus carrying the S227N change alone or with the residue-158 glycosylation site removed showed reduced lethality and systemic spread in mice but not in domestic chickens. Wild-type VN1203 virus exhibited the greatest efficiency in systemic spread after intramuscular inoculation and in infection of mouse bone marrow-derived dendritic cells and conventional pulmonary dendritic cells. These results show that VN1203 HA glycoprotein confers pathogenicity by facilitating systemic spread in mice; they also suggest that a minor change in receptor binding domain may modulate the virulence of H5N1 viruses. © 2008 by The National Academy of Sciences of the USA.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAnimalsen_US
dc.subject.meshChickensen_US
dc.subject.meshDendritic Cells - Virologyen_US
dc.subject.meshGlycosylationen_US
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - Genetics - Physiologyen_US
dc.subject.meshInfluenza A Virus, H5n1 Subtype - Chemistry - Genetics - Pathogenicityen_US
dc.subject.meshMiceen_US
dc.subject.meshMutationen_US
dc.subject.meshNeuraminidase - Geneticsen_US
dc.subject.meshOrganisms, Genetically Modifieden_US
dc.subject.meshProtein Interaction Domains And Motifs - Geneticsen_US
dc.subject.meshReceptors, Virus - Metabolismen_US
dc.subject.meshVirulence - Geneticsen_US
dc.titleChanges in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spreaden_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.doi10.1073/pnas.0811052106en_US
dc.identifier.pmid19116267-
dc.identifier.scopuseid_2-s2.0-58549110104en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58549110104&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume106en_US
dc.identifier.issue1en_US
dc.identifier.spage286en_US
dc.identifier.epage291en_US
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000262263900053-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridAldridge, JR=26021046700en_US
dc.identifier.scopusauthoridBoon, ACM=7006466647en_US
dc.identifier.scopusauthoridIlyushina, NA=6506741015en_US
dc.identifier.scopusauthoridSalomon, R=12786463900en_US
dc.identifier.scopusauthoridHulsePost, DJ=11940084300en_US
dc.identifier.scopusauthoridMarjuki, H=14018263900en_US
dc.identifier.scopusauthoridFranks, J=12786180500en_US
dc.identifier.scopusauthoridBoltz, DA=15019071200en_US
dc.identifier.scopusauthoridBush, D=7101925854en_US
dc.identifier.scopusauthoridLipatov, AS=7005117347en_US
dc.identifier.scopusauthoridWebby, RJ=35448064800en_US
dc.identifier.scopusauthoridRehg, JE=7004835777en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.identifier.citeulike3861388-

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