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

Abstract
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.
AuthorsNetanel Tzarum, Robert P de Vries, Xueyong Zhu, Wenli Yu, Ryan McBride, James C Paulson, Ian A Wilson
JournalCell host & microbe (Cell Host Microbe) Vol. 17 Issue 3 Pg. 369-376 (Mar 11 2015) ISSN: 1934-6069 [Electronic] United States
PMID25766295 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Virus
  • Sialic Acids
Topics
  • Amino Acid Substitution
  • Crystallography, X-Ray
  • Hemagglutinin Glycoproteins, Influenza Virus (chemistry, genetics, metabolism)
  • Humans
  • Influenza A virus (chemistry, genetics, isolation & purification, physiology)
  • Influenza, Human (virology)
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Receptors, Virus (chemistry, metabolism)
  • Sialic Acids (chemistry, metabolism)
  • Virus Attachment

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