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A Miniaturized Glycan Microarray Assay for Assessing Avidity and Specificity of Influenza A Virus Hemagglutinins
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The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus

Netanel Tzarum1, Robert P de Vries2, Wenjie Peng3

  • 1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Cell Reports
|April 14, 2017
PubMed

Insights

Avian influenza H10N8 viruses can adapt to humans. Mutations in the hemagglutinin’s 150-loop are key to avian influenza viruses gaining human receptor-binding ability, informing pandemic threat assessment.

Area of Science:

  • Virology
  • Molecular Biology
  • Public Health

Background:

  • Influenza A virus adaptation to new hosts is rare but can lead to pandemics.
  • Human infection with avian H10N8 influenza A virus occurred in 2013.
  • The hemagglutinin (HA) of H10N8 retains avian receptor specificity.

Purpose of the Study:

  • To investigate the molecular mechanisms enabling avian influenza viruses to adapt to human hosts.
  • To understand the role of the hemagglutinin 150-loop in receptor specificity.

Main Methods:

  • Site-directed mutagenesis of the H10 hemagglutinin 150-loop.
  • Introduction of mutations associated with human receptor binding (Q226L, G228S).
  • Structural analysis using crystal structures, receptor-binding assays, and tissue staining.

Main Results:

  • The 150-loop of H10 HA contains a two-residue insert potentially hindering human receptor binding.
  • Mutations in the 150-loop, combined with Q226L and G228S, conferred human-type receptor specificity.
  • Structural and binding studies confirmed the 150-loop's critical role in H10 receptor specificity.

Conclusions:

  • The 150-loop is a crucial determinant for avian influenza virus adaptation to human respiratory tissues.
  • Understanding these adaptations is vital for predicting and mitigating future influenza pandemic threats.
Keywords:
150-loopH10N8HAcrystal structureglycan arrayhemagglutininhost specificityinfluenza A virus

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