A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

Heng Zhang, Robert P. De Vries, Netanel Tzarum, Xueyong Zhu, Wenli Yu, Ryan McBride, James C. Paulson*, Ian A. Wilson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8 contains adaptations supporting human infection remains incompletely understood. We investigated whether H10N8 HA can bind human receptors. Sialoside glycan microarray analysis showed that the H10 HA retains a strong preference for avian receptor analogs and negligible binding to human receptor analogs. Crystal structures of H10 HA with avian and human receptor analogs revealed the basis for preferential recognition of avian-like receptors. Furthermore, introduction of mutations into the H10 receptor-binding site (RBS) known to convert other HA subtypes from avian to human receptor specificity failed to switch preference to human receptors. Collectively, these findings suggest that the current H10N8 human isolates are poorly adapted for efficient human-to-human transmission.

Original languageAmerican English
Pages (from-to)377-384
Number of pages8
JournalCell Host and Microbe
Issue number3
StatePublished - 11 Mar 2015
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded in part by NIH Grants R56 AI099275 (to I.A.W.) and AI099274 (to J.C.P.). R.P.d.V. is a recipient of Rubicon and VENI grants from the Netherlands Organization for Scientific Research (NWO) . We thank Robyn Stanfield, X. Dai, and M. Elsliger for crystallographic and computational support, Henry Tien of the Robotics Core at the Joint Center for Structural Genomics for automated crystal screening, and staff at the Stanford Synchrotron Radiation Lightsource (SSRL) beamlines 11-1 and 12-2. GM/CA CAT is funded in whole or in part with federal funds from the National Cancer Institute ( Y1-CO-1020 ) and NIGMS ( Y1-GM-1104 ). The SSRL is a Directorate of Stanford Linear Accelerator Center National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. DOE Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by NIH, NIGMS (including P41GM103393 ) and National Center for Research Resources (NCRR, P41RR001209 ). Several glycans used for HA binding assays were provided by the Consortium for Functional Glycomics ( http://www.functionalglycomics.org/ ) funded by NIGMS grant GM62116 (J.C.P.) We acknowledge the authors and the originating and submitting laboratories for HA sequences obtained from GISAID’s EpiFlu Database and from the influenza database of the NCBI.

Publisher Copyright:
© 2015 Elsevier Inc.


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