Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors

Shinya Yamada, Yasuo Suzuki, Takashi Suzuki, Mai Q. Le, Chairul A. Nidom, Yuko Sakai-Tagawa, Yukiko Muramoto, Mutsumi Ito, Maki Kiso, Taisuke Horimoto, Kyoko Shinya, Toshihiko Sawada, Makoto Kiso, Taiichi Usui, Takeomi Murata, Yipu Lin, Alan Hay, Lesley F. Haire, David J. Stevens, Rupert J. RussellSteven J. Gamblin, John J. Skehel, Yoshihiro Kawaoka

Research output: Contribution to journalArticlepeer-review

531 Citations (Scopus)

Abstract

H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects. Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-α2,6- galactose (SAα2,6Gal), whereas the latter prefer those ending in SAα2,3Gal (refs 3-6). A conversion from SAα2,3Gal to SAα2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor-binding haemagglutinin (HA) molecule that would enable avian H5N1 viruses to recognize human-type host cell receptors, it may be possible to predict (and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.

Original languageEnglish
Pages (from-to)378-382
Number of pages5
JournalNature
Volume444
Issue number7117
DOIs
Publication statusPublished - 16 Nov 2006

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