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Analysis: Nature: Receptor Binding Of H7N9

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  • Analysis: Nature: Receptor Binding Of H7N9

    Monday, October 28, 2013

    Nature: Receptor Binding Of H7N9

    Flu Virus binding to Receptor Cells ? Credit CDC

    # 7909

    For an influenza virus to infect a host, the virus must bind (attach) itself to the surface of a cell. To do that influenza viruses have an RBS - Receptor Binding Site (the area of its genetic sequence that allows it to attach to, and infect, host cells) that ? like a key slipping into a padlock -`fit? the host?s receptor cells.
    Avian adapted flu viruses, like the H5N1 virus, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds. While there are some alpha 2,3 cells deep in the lungs of humans, for an influenza to be successful in a human host, most researchers believe it needs to a able to bind to the α2-6 receptor cell found in the upper airway (trachea).
    We?ve seen studies over the summer that the emerging H7N9 virus in China ? unlike the H5N1 virus ? has shown signs of adapting to mammalian physiology (see Nature: Biological Features Of H7N9). Among the findings:

    • Unlike the H5N1 virus ? which binds preferentially to avian receptor cells (a2,3-linked sialic acid) - H7N9 binds to both the avian and human (a2,6-linked sialic acid) receptor cells.

    • This dual receptor cell binding ability likely enhances the virus?s ability to transmit from birds to humans.

    • The virus appears to replicate well in the lower human respiratory tract - but less well in the trachea ? which may have helped to limit its ability to spread from human-to-human.

    • Once infected, the virus often produces severe illness in humans, and patients tested showed increased serum levels of chemokines and cytokines, suggesting the possibility of infection inducing a `cytokine storm?.

    • There appears to be little or no community immunity to H7 viruses.

    Today, we?ve another study appearing in the Journal Nature that looks at the ability of the H7N9 virus to bind to human receptor cells (in vitro), that finds the virus better adapted to human receptor cells than earlier H7N9 viruses, but perhaps still not quite ready for prime time.

    Adaptation of novel H7N9 influenza A virus to human receptors

    J. C. F. M. Dortmans, J. Dekkers, I. N. Ambepitiya Wickramasinghe, M. H. Verheije, P. J. M. Rottier, F. J. M. van Kuppeveld, E. de Vries & C. A. M. de Haan
    The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.

    The entire study is open-access, and quite detailed regarding methods and materials. The authors sum up their findings in the discussion:
    The results indicate that, in comparison to avian H7N9 virus, the human H7N9 virus displays increased binding to α2-6 as well as α2-8 sialosides and reduced binding to α2-3-linked SIAs. Still, whereas all seasonal/pandemic IAVs bind more efficiently to α2-6- than to α2-3-linked sialosides, the human H7 protein binds more efficiently to α2-3- than α2-6-linked SIAs and is not able to efficiently bind to epithelial cells of human trachea. From these results we conclude that the human H7N9 virus has not (yet) adapted its HA protein to such an extent that it results in a receptor-binding profile similar to that of pandemic/seasonal IAV.
    For more on the evaluation of the emerging H7N9 virus, you may wish to revisit:
    Posted by Michael Coston at <a class="timestamp-link" href="" rel="bookmark" title="permanent link"><abbr class="published" itemprop="datePublished" title="2013-10-28T07:59:00-04:00">7:59 AM</abbr>