Structure and receptor binding of the hemagglutinin from a human H6N1 influenza virus

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Avian influenza viruses that cause infection and are transmissible in humans involve changes in the receptor binding site (RBS) of the viral hemagglutinin (HA) that alter receptor preference from α2-3-linked (avian-like) to α2-6-linked (human-like) sialosides. A human case of avian-origin H6N1 influenza virus was recently reported, but the molecular mechanisms contributing to it crossing the species barrier are unknown. We find that, although the H6 HA RBS contains D190V and G228S substitutions that potentially promote human receptor binding, recombinant H6 HA preferentially binds α2-3-linked sialosides, indicating no adaptation to human receptors. Crystal structures of H6 HA with avian and human receptor analogs reveal that H6 HA preferentially interacts with avian receptor analogs. This binding mechanism differs from other HA subtypes due to a unique combination of RBS residues, highlighting additional variation in HA-receptor interactions and the challenges in predicting which influenza strains and subtypes can infect humans and cause pandemics.

Original languageAmerican English
Pages (from-to)369-376
Number of pages8
JournalCell Host and Microbe
Issue number3
StatePublished - 11 Mar 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.


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