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A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors.

EMBO molecular medicine | 2017

In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcα2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcα2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding.

Pubmed ID: 28694323 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI114730
  • Agency: European Research Council, International
    Id: 280829
  • Agency: NCRR NIH HHS, United States
    Id: P41 RR001209
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI127371
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI117675
  • Agency: NIGMS NIH HHS, United States
    Id: U54 GM062116
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103393

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