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Article: Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets
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TitleHemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets
 
AuthorsYen, HL1
Liang, CH2
Wu, CY2
Forrest, HL3
Ferguson, A3
Choy, KT1
Jones, J3
Wong, DDY1
Cheung, PPH1
Hsu, CH2
Li, OT1
Yuen, KM1
Chan, RWY1
Poon, LLM1
Chan, MCW1
Nicholls, JM1
Krauss, S3
Wong, CH2
Guan, Y1
Webster, RG3
Webby, RJ3
Peiris, M1
 
KeywordsInfluenza A
Viral genes
Zoonosis
 
Issue Date2011
 
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
 
CitationProceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 34, p. 14264-14269 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.1111000108
 
AbstractA novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin-neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility.
 
ISSN0027-8424
2013 Impact Factor: 9.809
 
DOIhttp://dx.doi.org/10.1073/pnas.1111000108
 
PubMed Central IDPMC3161546
 
ISI Accession Number IDWOS:000294163500078
Funding AgencyGrant Number
Food and Health Bureau, Hong Kong
University Grants Committee, Hong KongAoE/M-12/06
University of Hong Kong
National Institute of Allergy and Infectious Diseases, National Institutes of HealthHHSN266200700005C
Funding Information:

We thank Dr. K. H. Chan for providing the pandemic H1N1 virus; Drs. G. J. D. Smith and D. Vijaykrishna for informative discussions; E. S. K. Ma, H. P. Chiu, and C. S. W. Leung, P. Seiler, K. Friedman, J. Franks, J. Turner, J. C. Crumpton, B. Marathe, A. Prevost, and D. Carey for technical assistance; and S. Naron for manuscript editing. This study was supported by the Research Fund for the Control of Infectious Diseases Commissioned Project from the Food and Health Bureau, Hong Kong; the Area of Excellence Scheme of the University Grants Committee (AoE/M-12/06), Hong Kong; Seed Funding for Basic Research, University of Hong Kong; and Contract HHSN266200700005C from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

 
ReferencesReferences in Scopus
 
GrantsControl of Pandemic and Inter-pandemic Influenza
 
DC FieldValue
dc.contributor.authorYen, HL
 
dc.contributor.authorLiang, CH
 
dc.contributor.authorWu, CY
 
dc.contributor.authorForrest, HL
 
dc.contributor.authorFerguson, A
 
dc.contributor.authorChoy, KT
 
dc.contributor.authorJones, J
 
dc.contributor.authorWong, DDY
 
dc.contributor.authorCheung, PPH
 
dc.contributor.authorHsu, CH
 
dc.contributor.authorLi, OT
 
dc.contributor.authorYuen, KM
 
dc.contributor.authorChan, RWY
 
dc.contributor.authorPoon, LLM
 
dc.contributor.authorChan, MCW
 
dc.contributor.authorNicholls, JM
 
dc.contributor.authorKrauss, S
 
dc.contributor.authorWong, CH
 
dc.contributor.authorGuan, Y
 
dc.contributor.authorWebster, RG
 
dc.contributor.authorWebby, RJ
 
dc.contributor.authorPeiris, M
 
dc.date.accessioned2011-10-28T02:45:21Z
 
dc.date.available2011-10-28T02:45:21Z
 
dc.date.issued2011
 
dc.description.abstractA novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin-neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 34, p. 14264-14269 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.1111000108
 
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.1111000108
 
dc.identifier.eissn1091-6490
 
dc.identifier.epage14269
 
dc.identifier.hkuros196694
 
dc.identifier.isiWOS:000294163500078
Funding AgencyGrant Number
Food and Health Bureau, Hong Kong
University Grants Committee, Hong KongAoE/M-12/06
University of Hong Kong
National Institute of Allergy and Infectious Diseases, National Institutes of HealthHHSN266200700005C
Funding Information:

We thank Dr. K. H. Chan for providing the pandemic H1N1 virus; Drs. G. J. D. Smith and D. Vijaykrishna for informative discussions; E. S. K. Ma, H. P. Chiu, and C. S. W. Leung, P. Seiler, K. Friedman, J. Franks, J. Turner, J. C. Crumpton, B. Marathe, A. Prevost, and D. Carey for technical assistance; and S. Naron for manuscript editing. This study was supported by the Research Fund for the Control of Infectious Diseases Commissioned Project from the Food and Health Bureau, Hong Kong; the Area of Excellence Scheme of the University Grants Committee (AoE/M-12/06), Hong Kong; Seed Funding for Basic Research, University of Hong Kong; and Contract HHSN266200700005C from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

 
dc.identifier.issn0027-8424
2013 Impact Factor: 9.809
 
dc.identifier.issue34
 
dc.identifier.pmcidPMC3161546
 
dc.identifier.pmid21825167
 
dc.identifier.scopuseid_2-s2.0-80052186216
 
dc.identifier.spage14264
 
dc.identifier.urihttp://hdl.handle.net/10722/142404
 
dc.identifier.volume108
 
dc.languageeng
 
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
 
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshFerrets - virology
 
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - metabolism
 
dc.subject.meshInfluenza A Virus, H1N1 Subtype - enzymology - genetics - physiology
 
dc.subject.meshNeuraminidase - metabolism
 
dc.subject.meshOrthomyxoviridae Infections - epidemiology - transmission - virology
 
dc.subjectInfluenza A
 
dc.subjectViral genes
 
dc.subjectZoonosis
 
dc.titleHemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Genomics Research Center, Academia Sinica
  3. St. Jude Children Research Hospital