The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus

Publication date: 11 April 2017
Source:Cell Reports, Volume 19, Issue 2
Author(s): Netanel Tzarum, Robert P. de Vries, Wenjie Peng, Andrew J. Thompson, Kim M. Bouwman, Ryan McBride, Wenli Yu, Xueyong Zhu, Monique H. Verheije, James C. Paulson, Ian A. Wilson
Adaptation of influenza A viruses to new hosts are rare events but are the basis for emergence of new influenza pandemics in the human population. Thus, understanding the processes involved in such events is critical for anticipating potential pandemic threats. In 2013, the first case of human infection by an avian H10N8 virus was reported, yet the H10 hemagglutinin (HA) maintains avian receptor specificity. However, the 150-loop of H10 HA, as well as related H7 and H15 subtypes, contains a two-residue insert that can potentially block human receptor binding. Mutation of the 150-loop on the background of Q226L and G228S mutations, which arose in the receptor-binding site of human pandemic H2 and H3 viruses, resulted in acquisition of human-type receptor specificity. Crystal structures of H10 HA mutants with human and avian receptor analogs, receptor-binding studies, and tissue staining experiments illustrate the important role of the 150-loop in H10 receptor specificity.

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Introduction and subsequent circulation of avian and other zoonotic influenza viruses in the human population requires changes to the hemagglutinin-binding specificity. Tzarum et al. report on mutations that can alter the receptor specificity of hemagglutinin H10 using a glycan array, tissue staining, and structural analysis.


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