Science for Health
21 June 2013
Over the past few months influenza viruses from birds caused infections of humans in several eastern provinces of China. By 30 May 2013 there were 132 confirmed cases with 37 deaths. The WHO Collaborating Centre for Reference and Research in Beijing characterised the virus as an H7N9 virus with all its genes derived from avian influenza viruses. The genes for the haemagglutinin (HA) and neuraminidase (NA) virus membrane glycoproteins are similar to those from viruses recently isolated from ducks and wild birds from China and Korea. The rest of their genomes derived from H9N2 viruses that have circulated widely in birds in the Far East and the Middle East since the late 1990s, causing sporadic human infections.
The sequence of the HA gene of H7N9 virus isolated from both humans and birds had unusual features that suggested that the interaction of the virus with its sialic acid receptor was unusual for such an avian influenza virus.
Steve Gamblin (pictured), John Skehel, John McCauley (Director of NIMR's WHO Influenza Centre), Xiaoli Xiong, Stephen Martin, Steve Wharton and their colleagues, measured the binding of human H7N9 and avian H7N3 viruses to biosensors coated with human and avian receptor analogues. They showed that the H7N9 virus had significantly higher affinity for a-2,6-linked sialic acid analogues (‘human receptor’) than an H7 HA from the avian virus, while retaining the strong binding to a-2,3-linked sialic acid analogues (‘avian receptor’) characteristic of avian viruses. The new H7N9 virus seems not to have the characteristic preference, for human versus avian receptors, that other pandemic viruses have.
X-ray crystallography of the HA in complex with receptor analogues indicated that both human and avian receptors adopt different conformations when bound to human H7 HA compared with the conformation bound to a typical avian H7 HA. The studies showed that the human receptor bound to human H7 HA exits the binding site in a different direction from that seen in complexes formed by HAs from pandemic viruses. The human-receptor-binding properties of human H7 probably arise from the introduction of two bulky hydrophobic residues by the substitutions Gln226Leu and Gly186Val, the former being shared with the 1957 H2 and 1968 H3 pandemic viruses.
These results indicate that the human H7 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses but retains a preference for avian receptor. This suggests that efficient transmission of the virus between humans might be restricted, perhaps by binding to avian-receptor rich mucins in the human respiratory tract rather than to cellular receptors.
The increase in the number of human cases in China has stopped and surveillance of poultry markets has revealed only a small number of affected premises. H7N9 seems to be under control and present but, nevertheless, H7N9 viruses still pose a pandemic threat.
Xiaoli Xiong, Stephen R. Martin, Lesley F. Haire, Stephen A. Wharton, Rodney S. Daniels, Michael S. Bennett, John W. McCauley, Patrick J. Collins, Philip A. Walker, John J. Skehel & Steven J. Gamblin (2013)
Receptor binding by an H7N9 influenza virus from humans
Nature, epub ahead of print. Publisher abstract.
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA