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Title: 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. Lastly, 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.

Authors:
 [1];  [2];  [1];  [1];  [2];  [2];  [3]
  1. Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology
  2. Scripps Research Inst., La Jolla, CA (United States). Dept. of Cell and Molecular Biology; Scripps Research Inst., La Jolla, CA (United States). Dept. of Chemical Physiology; Scripps Research Inst., La Jolla, CA (United States). Dept. of Immunology and Microbial Science
  3. Scripps Research Inst., La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology; Scripps Research Inst., La Jolla, CA (United States). Skaggs Inst. for Chemical Biology
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)
OSTI Identifier:
1241403
Alternate Identifier(s):
OSTI ID: 1182314; OSTI ID: 1233923
Grant/Contract Number:  
AC02-06CH11357; R56 AI099275; AI099274; U54 GM094586; Y1-GM-1104; Y1-CO-1020
Resource Type:
Journal Article: Published Article
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 17; Journal Issue: 3; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Tzarum, Netanel, de Vries, Robert P., Zhu, Xueyong, Yu, Wenli, McBride, Ryan, Paulson, James C., and Wilson, Ian A. Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus. United States: N. p., 2015. Web. doi:10.1016/j.chom.2015.02.005.
Tzarum, Netanel, de Vries, Robert P., Zhu, Xueyong, Yu, Wenli, McBride, Ryan, Paulson, James C., & Wilson, Ian A. Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus. United States. doi:10.1016/j.chom.2015.02.005.
Tzarum, Netanel, de Vries, Robert P., Zhu, Xueyong, Yu, Wenli, McBride, Ryan, Paulson, James C., and Wilson, Ian A. Wed . "Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus". United States. doi:10.1016/j.chom.2015.02.005.
@article{osti_1241403,
title = {Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus},
author = {Tzarum, Netanel and de Vries, Robert P. and Zhu, Xueyong and Yu, Wenli and McBride, Ryan and Paulson, James C. and Wilson, Ian A.},
abstractNote = {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. Lastly, 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.},
doi = {10.1016/j.chom.2015.02.005},
journal = {Cell Host & Microbe},
number = 3,
volume = 17,
place = {United States},
year = {Wed Mar 11 00:00:00 EDT 2015},
month = {Wed Mar 11 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.chom.2015.02.005

Citation Metrics:
Cited by: 16 works
Citation information provided by
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