Proc Natl Acad Sci USA. Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets

[Giuseppe]

[Source: Proc Natl Acad Sci USA, full text: (LINK). Abstract, edited.]

Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets [Microbiology]



Yen, H.-L., Liang, C.-H., Wu, C.-Y., Forrest, H. L., Ferguson, A., Choy, K.-T., Jones, J., Dik-Yan Wong, D., Pak-Hang Cheung, P., Hsu, C.-H., Li, O. T., Yuen, K. M., Chan, R. W. Y., Poon, L. L. M., Chan, M. C. W., Nicholls, J. M., Krauss, S., Wong, C.-H., Guan, Y., Webster, R. G., Webby, R. J., Peiris, M.

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.

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Re: Proc Natl Acad Sci USA. Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets

Key link found to swine flu in humans

Hong Kong researchers claim a major breakthrough in establishing how swine flu spreads from animals to humans.

The research, led by Li Ka Shing Faculty of Medicine at Hong Kong University, was published in the Proceedings of the National Academy of Sciences, a respected US journal.

The team used ferrets as animal models to take advantage of the transmission similarities between ferrets and humans.

"There are two significant points for this new discovery," said Professor Malik Peiris from HKU.

"First is that it allows us to identify a virus with potential ability to transmit from animals to humans. Then we can focus on them instead of tackling all viruses."
Most animal viruses are found incapable of transmitting from animals to humans. . . .

The research team discovered that once a balance is achieved between two specific virus surface proteins, namely haemagglutinin and neuraminidase, a swine influenza virus then gains the "ability to transmit efficiently" through the air.

"Second, this discovery can guide us to our next stop of the research. In the long term, understanding the mechanism of the virus transmission will help to tackle the pandemic transmission," said Peiris. . . .

http://www.chinadaily.com.cn/hkedition/2011-08/10/content_13081289.htm