Science for Health
20 June 2014
The influenza H10N8 virus is the latest in a line of avian flu viruses that cause serious disease in humans, following H7N9 and H5N1. The first human H10N8 infection was detected in a fatal case of pneumonia in December 2013 in China. Since then, there have been two further cases of avian H10N8 infection, and an additional death.
Steve Gamblin (pictured) and his team from NIMR's Division of Molecular Structure has collaborated with NIMR’s WHO Influenza Centre to investigate whether H10 viruses had the potential to cause a pandemic. They determined the structure of the haemagglutinin of a previously isolated avian H10 virus and looked at its receptor binding properties, as the strength of the interaction between virus and host is a major factor in determining the likelihood of an animal strain of influenza virus becoming causing a pandemic. They found that although the H10 influenza virus bound strongly to human receptors, it attached more tightly to avian receptors. They believe that for H10N8 to pose a threat to human health it would need to lose some of its binding capacity for avian receptors.
The binding characteristics of H10 are shared with other pandemic strains of influenza such as H1 (1918 Spanish flu) and with recent H7 viruses that have infected humans. However, the H1 and other pandemic viruses have a clear preference for human receptors, binding to them up to 100 times more tightly than to avian receptors. With the H10 strain, the interaction with the avian receptor is approximately 150 times stronger than with the human receptor.
The recent H10N8 strain of bird flu is unlikely to result in a public health threat without further mutations in the virus that would allow it to spread between humans. In terms of surveillance, particular attention will be paid to the detection of mutations in the receptor-binding site of the H10 haemagglutinin that decrease its avidity for avian receptor and could enable it to be more readily transmitted between humans. A change in receptor binding is the essential first step in generating a pandemic virus.
These results are the output of the NIMR/WHO Influenza Centre collaboration that illustrates the sophisticated scientific basis of monitoring influenza viruses and the importance of the WHO global influenza surveillance for public health.
John McCauley, Director of the WHO Influenza Centre
Click image to view at full-size
The receptor-binding site of H10 is bounded by the 130- and 220-loops and the 190-helix. The site is shown as a ribbons cartoon, with the receptors shown in stick representation, together with electron density from a 2Fo – Fc Fourier map contoured at 0.8σ. The human receptor complex of H10 shows the second and third sugars exiting the binding site across the 130-loop.
Sebastien G. Vachieri, Xiaoli Xiong, Patrick J. Collins, Philip A.Walker, Stephen R. Martin, Lesley F. Haire, Ying Zhang, John W. McCauley, Steven J. Gamblin & John J. Skehel. (2014)
Receptor binding by H10 influenza viruses.
Nature. doi:10.1038/nature13443. Article full-text
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