The soft palate is an important site of adaptation for transmissible influenza viruses

Article

关键词: HUMAN RESPIRATORY-TRACT;    AIRBORNE TRANSMISSION;    RECEPTOR SPECIFICITY;    A/H5N1 VIRUS;    IN-VITRO;    A VIRUS;    FERRETS;    H1N1;    HEMAGGLUTININ;    PATHOGENESIS;   

DOI  :  10.1038/nature15379

来源: SCIE

【 摘 要 】

Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached alpha 2,3 or alpha 2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind alpha 2,6-linked sialic acids whereas avian influenza A viruses bind alpha 2,3-linked sialic acids on complex glycans on airway epithelial cells(1,2). Historically, influenza A viruses with preferential association with alpha 2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets(3,4). Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind alpha 2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain alpha 2,6-linked sialic acids, without loss of alpha 2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain alpha 2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain alpha 2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (alpha 2,6-linked sialic acids) preference.

【 授权许可】

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