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

• Autores: Seema S. Lakdawala, Akila Jayaraman, Rebecca Halpin, Elaine W. Lamirande, Angela R. Shih, Timothy B. Stockwell
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 526, Nº 7571, 2015, págs. 122-125
• Idioma: inglés
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• Resumen

  • 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 cells1,2. Historically, influenza A viruses with preferential association with [alpha]2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets3,4. 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.