Resumen de The soft palate is an important site of adaptation for transmissible influenza viruses
Seema S. Lakdawala, Akila Jayaraman, Rebecca Halpin, Elaine W. Lamirande, Angela R. Shih, Timothy B. Stockwell
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.
