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EMBO Mol Med. 2017 Sep;9(9):1314-1325. doi: 10.15252/emmm.201707726.

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

Author information

1
Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
2
Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
3
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, The Scripps Research Institute, La Jolla, CA, USA.
4
Pathology Division, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
5
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
6
Department of Microbiology and Immunology, Weil Medical College of Cornell University, New York, NY, USA.
7
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, The Scripps Research Institute, La Jolla, CA, USA wilson@scripps.edu jpaulson@scripps.edu.
8
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
9
Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA wilson@scripps.edu jpaulson@scripps.edu.

Abstract

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.

KEYWORDS:

X‐ray crystallography; glycan array; hemagglutinin; influenza A virus; sialic acid

PMID:
28694323
PMCID:
PMC5582370
DOI:
10.15252/emmm.201707726
[Indexed for MEDLINE]
Free PMC Article

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