The soft palate is an important site of adaptation for transmissible influenza viruses.
Nature, 2015/10/01;526(7571):122-5.
Lakdawala SS[1], Jayaraman A[2], Halpin RA[3], Lamirande EW[1], Shih AR[1], Stockwell TB[3], Lin X[3], Simenauer A[3], Hanson CT[1], Vogel L[1], Paskel M[1], Minai M[4], Moore I[4], Orandle M[4], Das SR[3], Wentworth DE[3], Sasisekharan R[2], Subbarao K[1]
Affiliations
PMID: 26416728DOI: 10.1038/nature15379
Impact factor: 69.504
Abstract
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 α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-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 α2,6-linked sialic acids, without loss of α2,3-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 α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-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 (α2,6-linked sialic acids) preference.
MeSH terms
Adaptation, Physiological; Animals; Epithelial Cells; Female; Ferrets; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza A Virus, H1N1 Subtype; Male; Molecular Sequence Data; Orthomyxoviridae Infections; Palate, Soft; Receptors, Virus; Respiratory System; Selection, Genetic; Sialic Acids; Swine
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