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Conference Paper: Transmission and pathogenicity of H5N1 influenza viruses

TitleTransmission and pathogenicity of H5N1 influenza viruses
Authors
Issue Date2008
PublisherJohn Wiley & Sons Ltd.
Citation
Proceedings of the Novartis Foundation Symposium, 2008, v. 290, p. 128-137 How to Cite?
AbstractThe interaction between multiple viral and host factors determine the pathogenicity and transmissibility of H5N1 influenza viruses. The viral surface glycoprotein haemagglutinin (HA) plays a crucial role in attachment to the host-cell sialic acid (SA) receptor and in viral growth and tissue tropism. Other viral factors known as host range or virulence determinants include viral polymerase, particularly residue 627 in the PB2 protein, and the ability to evade the host immune response through the viral NS1 protein. Applying plasmid-based reverse genetics, we have provided a good model system to study the molecular basis for pathogenicity. Differences in the pathogenicity in mammalian species were previously observed between human (A/Vietnam/1203/04) and chicken (A/Chicken/Vietnam/C58/04) H5N1 isolates. Detailed molecular characterization by plasmid-based reverse genetics showed that the polymerase subunits PB1 and PB2 contribute to the lethality of A/Vietnam/1203/04. The polymerase complex possessed significantly higher transcription/replication activity than the A/Chicken/Vietnam/C58/04 polymerase complex. Our results suggest that high polymerase activity acts as a molecular determinant for virulence in mammalian species. We also evaluated the transmissibility and pathogenicity of H5N1 viruses isolated from humans during the years 2003-2006 using a ferret contact model comprising one inoculated and two contact ferrets. This animal model has been shown to support efficient transmission of seasonal human influenza viruses. At 103 TCID50, A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which have 'avian-like' α2,3-linked SA receptor affinity, caused neurological symptoms and death in ferrets. A/HongKong/213/03 and A/Turkey/65-596/06 viruses, which have affinity for both 'human-like' (α2,6-linked) and 'avian-like' SA receptors, caused mild clinical symptoms and were not lethal to ferrets. No transmission of A/Vietnam/1203/04 and A/Turkey/65-596/06 viruses was detected, and transmission of A/HongKong/213/03 and A/Vietnam/JP36-2/05 viruses was inefficient. These results demonstrate that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammals. Copyright © Novartis Foundation 2008.
Persistent Identifierhttp://hdl.handle.net/10722/179860
ISBN
ISSN
2004 Impact Factor: 1.879
2011 SCImago Journal Rankings: 0.267
References

 

DC FieldValueLanguage
dc.contributor.authorHoffmann, Een_US
dc.contributor.authorYen, HLen_US
dc.contributor.authorSalomon, Ren_US
dc.contributor.authorYilmaz, Nen_US
dc.contributor.authorWebster, RGen_US
dc.date.accessioned2012-12-19T10:06:14Z-
dc.date.available2012-12-19T10:06:14Z-
dc.date.issued2008en_US
dc.identifier.citationProceedings of the Novartis Foundation Symposium, 2008, v. 290, p. 128-137en_US
dc.identifier.isbn978-047006538-9-
dc.identifier.issn1528-2511en_US
dc.identifier.urihttp://hdl.handle.net/10722/179860-
dc.description.abstractThe interaction between multiple viral and host factors determine the pathogenicity and transmissibility of H5N1 influenza viruses. The viral surface glycoprotein haemagglutinin (HA) plays a crucial role in attachment to the host-cell sialic acid (SA) receptor and in viral growth and tissue tropism. Other viral factors known as host range or virulence determinants include viral polymerase, particularly residue 627 in the PB2 protein, and the ability to evade the host immune response through the viral NS1 protein. Applying plasmid-based reverse genetics, we have provided a good model system to study the molecular basis for pathogenicity. Differences in the pathogenicity in mammalian species were previously observed between human (A/Vietnam/1203/04) and chicken (A/Chicken/Vietnam/C58/04) H5N1 isolates. Detailed molecular characterization by plasmid-based reverse genetics showed that the polymerase subunits PB1 and PB2 contribute to the lethality of A/Vietnam/1203/04. The polymerase complex possessed significantly higher transcription/replication activity than the A/Chicken/Vietnam/C58/04 polymerase complex. Our results suggest that high polymerase activity acts as a molecular determinant for virulence in mammalian species. We also evaluated the transmissibility and pathogenicity of H5N1 viruses isolated from humans during the years 2003-2006 using a ferret contact model comprising one inoculated and two contact ferrets. This animal model has been shown to support efficient transmission of seasonal human influenza viruses. At 103 TCID50, A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which have 'avian-like' α2,3-linked SA receptor affinity, caused neurological symptoms and death in ferrets. A/HongKong/213/03 and A/Turkey/65-596/06 viruses, which have affinity for both 'human-like' (α2,6-linked) and 'avian-like' SA receptors, caused mild clinical symptoms and were not lethal to ferrets. No transmission of A/Vietnam/1203/04 and A/Turkey/65-596/06 viruses was detected, and transmission of A/HongKong/213/03 and A/Vietnam/JP36-2/05 viruses was inefficient. These results demonstrate that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammals. Copyright © Novartis Foundation 2008.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd.-
dc.relation.ispartofNovartis Foundation Symposiumen_US
dc.titleTransmission and pathogenicity of H5N1 influenza virusesen_US
dc.typeConference_Paperen_US
dc.identifier.emailYen, HL: hyen@hku.hken_US
dc.identifier.authorityYen, HL=rp00304en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.scopuseid_2-s2.0-56249124935en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56249124935&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume290en_US
dc.identifier.spage128en_US
dc.identifier.epage137en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridHoffmann, E=7201369718en_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridSalomon, R=12786463900en_US
dc.identifier.scopusauthoridYilmaz, N=16647702000en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.customcontrol.immutablesml 160519 amended-

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