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Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets.
Proc Natl Acad Sci U S A. 2011 Aug 23; 108(34):14264-9.PN

Abstract

A 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.

Authors+Show Affiliations

Department of Microbiology, HKU-Pasteur Research Centre, University of Hong Kong, Pokfulam, Hong Kong SAR, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21825167

Citation

Yen, Hui-Ling, et al. "Hemagglutinin-neuraminidase Balance Confers Respiratory-droplet Transmissibility of the Pandemic H1N1 Influenza Virus in Ferrets." Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 34, 2011, pp. 14264-9.
Yen HL, Liang CH, Wu CY, et al. Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets. Proc Natl Acad Sci USA. 2011;108(34):14264-9.
Yen, H. L., Liang, C. H., Wu, C. Y., Forrest, H. L., Ferguson, A., Choy, K. T., Jones, J., Wong, D. D., Cheung, P. P., Hsu, C. H., Li, O. T., Yuen, K. M., Chan, R. W., Poon, L. L., Chan, M. C., Nicholls, J. M., Krauss, S., Wong, C. H., Guan, Y., ... Peiris, M. (2011). Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets. Proceedings of the National Academy of Sciences of the United States of America, 108(34), 14264-9. https://doi.org/10.1073/pnas.1111000108
Yen HL, et al. Hemagglutinin-neuraminidase Balance Confers Respiratory-droplet Transmissibility of the Pandemic H1N1 Influenza Virus in Ferrets. Proc Natl Acad Sci USA. 2011 Aug 23;108(34):14264-9. PubMed PMID: 21825167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets. AU - Yen,Hui-Ling, AU - Liang,Chi-Hui, AU - Wu,Chung-Yi, AU - Forrest,Heather L, AU - Ferguson,Angela, AU - Choy,Ka-Tim, AU - Jones,Jeremy, AU - Wong,Diana Dik-Yan, AU - Cheung,Peter Pak-Hang, AU - Hsu,Che-Hsiung, AU - Li,Olive T, AU - Yuen,Kit M, AU - Chan,Renee W Y, AU - Poon,Leo L M, AU - Chan,Michael C W, AU - Nicholls,John M, AU - Krauss,Scott, AU - Wong,Chi-Huey, AU - Guan,Yi, AU - Webster,Robert G, AU - Webby,Richard J, AU - Peiris,Malik, Y1 - 2011/08/08/ PY - 2011/8/10/entrez PY - 2011/8/10/pubmed PY - 2011/10/28/medline SP - 14264 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 108 IS - 34 N2 - A 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/21825167/Hemagglutinin_neuraminidase_balance_confers_respiratory_droplet_transmissibility_of_the_pandemic_H1N1_influenza_virus_in_ferrets_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=21825167 DB - PRIME DP - Unbound Medicine ER -