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Neuraminidase activity and specificity of influenza A virus are influenced by haemagglutinin-receptor binding

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  • Neuraminidase activity and specificity of influenza A virus are influenced by haemagglutinin-receptor binding

    Emerg Microbes Infect. 2019;8(1):327-338. doi: 10.1080/22221751.2019.1581034.
    Neuraminidase activity and specificity of influenza A virus are influenced by haemagglutinin-receptor binding.

    Lai JCC1,2, Karunarathna HMTK3,4, Wong HH1,2, Peiris JSM2,3, Nicholls JM1.
    Author information

    Abstract

    Influenza virus haemagglutinin (HA) and neuraminidase (NA) are involved in the recognition and modulation of sialic acids on the cell surface as the virus receptor. Although the balance between two proteins functions has been found to be crucial for viral fitness, the interplay between the proteins has not been well established. Herein we present evidence for interplay between influenza HA and NA, which may affect the balance between two glycoprotein functions. NA enzymatic activities against sialoglycans were promoted by the presence of HA, which is in accordance with the level of co-existing HA. Such activity enhancement was lost when the HA-receptor binding properties were abolished by low-pH treatment or by mutations at the HA receptor binding domain. Sialidase activities of NA-containing virus-like particles and native influenza viruses were detected using different NA-assays and sialic acid substrates. Most pronounced HA-mediated NA enhancement was found when intact virions were confronted with multivalent surface-anchored substrates, which mimics the physiological conditions on cell membranes. Using recombinant viruses with altered HA bindings preference between α2,3- and α2,6-linked sialic acids, we also found that NA function against different substrates is correlated with the HA-receptor specificity. The effect of HA-receptor specificities on NA functions, together with the HA-mediated NA enhancement, may play a role in virus evasion of the mucus barrier, as well as in cross-species adaptation. Our data also indicate the importance of using multivalent substrates in future studies of NA functions.


    KEYWORDS:

    Hemagglutinin; Influenza virus; neuraminidase; receptor interaction; sialic acids

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