skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses

Abstract

The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that, compared to the 2013 virus HAs, the fifth-wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9) HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth-wave H7 HAs analyzed in this study. IMPORTANCEThe A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins frommore » several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHER
OSTI Identifier:
1463715
Resource Type:
Journal Article
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 92; Journal Issue: 16; Journal ID: ISSN 0022-538X
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Yang, Hua, Carney, Paul J., Chang, Jessie C., Guo, Zhu, Stevens, James, and Williams, Bryan R. G. Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses. United States: N. p., 2018. Web. doi:10.1128/JVI.00375-18.
Yang, Hua, Carney, Paul J., Chang, Jessie C., Guo, Zhu, Stevens, James, & Williams, Bryan R. G. Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses. United States. doi:10.1128/JVI.00375-18.
Yang, Hua, Carney, Paul J., Chang, Jessie C., Guo, Zhu, Stevens, James, and Williams, Bryan R. G. Wed . "Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses". United States. doi:10.1128/JVI.00375-18.
@article{osti_1463715,
title = {Structural and Molecular Characterization of the Hemagglutinin from the Fifth-Epidemic-Wave A(H7N9) Influenza Viruses},
author = {Yang, Hua and Carney, Paul J. and Chang, Jessie C. and Guo, Zhu and Stevens, James and Williams, Bryan R. G.},
abstractNote = {The avian influenza A(H7N9) virus continues to cause human infections in China and is a major ongoing public health concern. Five epidemic waves of A(H7N9) infection have occurred since 2013, and the recent fifth epidemic wave saw the emergence of two distinct lineages with elevated numbers of human infection cases and broader geographic distribution of viral diseases compared to the first four epidemic waves. Moreover, highly pathogenic avian influenza (HPAI) A(H7N9) viruses were also isolated during the fifth epidemic wave. Here, we present a detailed structural and biochemical analysis of the surface hemagglutinin (HA) antigen from viruses isolated during this recent epidemic wave. Results highlight that, compared to the 2013 virus HAs, the fifth-wave virus HAs remained a weak binder to human glycan receptor analogs. We also studied three mutations, V177K-K184T-G219S, that were recently reported to switch a 2013 A(H7N9) HA to human-type receptor specificity. Our results indicate that these mutations could also switch the H7 HA receptor preference to a predominantly human binding specificity for both fifth-wave H7 HAs analyzed in this study. IMPORTANCEThe A(H7N9) viruses circulating in China are of great public health concern. Here, we report a molecular and structural study of the major surface proteins from several recent A(H7N9) influenza viruses. Our results improve the understanding of these evolving viruses and provide important information on their receptor preference that is central to ongoing pandemic risk assessment.},
doi = {10.1128/JVI.00375-18},
journal = {Journal of Virology},
issn = {0022-538X},
number = 16,
volume = 92,
place = {United States},
year = {2018},
month = {5}
}

Works referenced in this record:

Receptor binding properties of human and animal H1 influenza virus isolates
journal, November 1989


Potential for transmission of avian influenza viruses to pigs
journal, September 1994


Development of Framework for Assessing Influenza Virus Pandemic Risk
journal, August 2015

  • Trock, Susan C.; Burke, Stephen A.; Cox, Nancy J.
  • Emerging Infectious Diseases, Vol. 21, Issue 8
  • DOI: 10.3201/eid2108.141086

Microbatch crystallization under oil — a new technique allowing many small-volume crystallization trials
journal, August 1992

  • Chayen, Naomi E.; Shaw Stewart, Patrick D.; Blow, David M.
  • Journal of Crystal Growth, Vol. 122, Issue 1-4
  • DOI: 10.1016/0022-0248(92)90241-A

Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation
journal, January 1981

  • Wiley, D. C.; Wilson, I. A.; Skehel, J. J.
  • Nature, Vol. 289, Issue 5796
  • DOI: 10.1038/289373a0

Structure and Receptor Complexes of the Hemagglutinin from a Highly Pathogenic H7N7 Influenza Virus
journal, June 2012

  • Yang, Hua; Carney, Paul J.; Donis, Ruben O.
  • Journal of Virology, Vol. 86, Issue 16
  • DOI: 10.1128/JVI.00281-12

Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses
journal, April 2011


Rapid adaptation of avian H7N9 virus in pigs
journal, March 2014


Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Use of TLS parameters to model anisotropic displacements in macromolecular refinement
journal, January 2001

  • Winn, M. D.; Isupov, M. N.; Murshudov, G. N.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 57, Issue 1
  • DOI: 10.1107/S0907444900014736

Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus
journal, September 2013

  • Yang, H.; Carney, P. J.; Chang, J. C.
  • Journal of Virology, Vol. 87, Issue 22
  • DOI: 10.1128/JVI.01854-13

The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus
journal, April 2017


Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses
journal, April 2016

  • Yang, Hua; Carney, Paul J.; Mishin, Vasiliy P.
  • Journal of Virology, Vol. 90, Issue 12
  • DOI: 10.1128/JVI.00180-16

Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic — China, October 1, 2016–August 7, 2017
journal, September 2017

  • Kile, James C.; Ren, Ruiqi; Liu, Liqi
  • MMWR. Morbidity and Mortality Weekly Report, Vol. 66, Issue 35
  • DOI: 10.15585/mmwr.mm6635a2

Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans
journal, May 2009


Epidemiology, Evolution, and Pathogenesis of H7N9 Influenza Viruses in Five Epidemic Waves since 2013 in China
journal, September 2017


Adaptation of novel H7N9 influenza A virus to human receptors
journal, October 2013

  • Dortmans, J. C. F. M.; Dekkers, J.; Wickramasinghe, I. N. Ambepitiya
  • Scientific Reports, Vol. 3, Issue 1
  • DOI: 10.1038/srep03058

Role of Substitutions in the Hemagglutinin in the Emergence of the 1968 Pandemic Influenza Virus
journal, September 2015

  • Van Poucke, Sjouke; Doedt, Jennifer; Baumann, Jan
  • Journal of Virology, Vol. 89, Issue 23
  • DOI: 10.1128/JVI.01292-15

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Clusters of Human Infection and Human-to-Human Transmission of Avian Influenza A(H7N9) Virus, 2013–2017
journal, February 2018

  • Zhou, Lei; Chen, Enfu; Bao, Changjun
  • Emerging Infectious Diseases, Vol. 24, Issue 2
  • DOI: 10.3201/eid2402.171565

Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China
journal, March 2016

  • Wang, Dayan; Yang, Lei; Zhu, Wenfei
  • Journal of Virology, Vol. 90, Issue 12
  • DOI: 10.1128/JVI.03173-15

Transmission of influenza A viruses
journal, May 2015


Structure and Receptor Binding Preferences of Recombinant Hemagglutinins from Avian and Human H6 and H10 Influenza A Virus Subtypes
journal, February 2015

  • Yang, Hua; Carney, Paul J.; Chang, Jessie C.
  • Journal of Virology, Vol. 89, Issue 8
  • DOI: 10.1128/JVI.03456-14

Genesis and Spread of Newly Emerged Highly Pathogenic H7N9 Avian Viruses in Mainland China
journal, September 2017

  • Yang, Lei; Zhu, Wenfei; Li, Xiyan
  • Journal of Virology, Vol. 91, Issue 23
  • DOI: 10.1128/JVI.01277-17

MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
journal, May 2007

  • Davis, I. W.; Leaver-Fay, A.; Chen, V. B.
  • Nucleic Acids Research, Vol. 35, Issue Web Server
  • DOI: 10.1093/nar/gkm216

Receptor Specificity in Human, Avian, and Equine H2 and H3 Influenza Virus Isolates
journal, November 1994

  • Connor, Robert J.; Kawaoka, Yoshihiro; Webster, Robert G.
  • Virology, Vol. 205, Issue 1
  • DOI: 10.1006/viro.1994.1615

On the origin of the human influenza virus subtypes H2N2 and H3N2
journal, June 1978


The origin of the 1918 pandemic influenza virus: a continuing enigma
journal, September 2003


The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin
journal, December 2001

  • Brownlee, G. G.; Fodor, E.
  • Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, Vol. 356, Issue 1416
  • DOI: 10.1098/rstb.2001.1001

Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model
journal, April 2007

  • Yen, H. -L.; Lipatov, A. S.; Ilyushina, N. A.
  • Journal of Virology, Vol. 81, Issue 13
  • DOI: 10.1128/JVI.00170-07

Host adaptation and transmission of influenza A viruses in mammals
journal, January 2014

  • Schrauwen, Eefje JA; Fouchier, Ron AM
  • Emerging Microbes & Infections, Vol. 3, Issue 1
  • DOI: 10.1038/emi.2014.9

Structures of Receptor Complexes of a North American H7N2 Influenza Hemagglutinin with a Loop Deletion in the Receptor Binding Site
journal, September 2010


In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity
journal, January 2012


Receptor binding by an H7N9 influenza virus from humans
journal, June 2013

  • Xiong, Xiaoli; Martin, Stephen R.; Haire, Lesley F.
  • Nature, Vol. 499, Issue 7459
  • DOI: 10.1038/nature12372

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets
journal, November 2017


Three mutations switch H7N9 influenza to human-type receptor specificity
journal, June 2017


Seasonality of Influenza A(H7N9) Virus in China—Fitting Simple Epidemic Models to Human Cases
journal, March 2016


Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors
journal, November 2006

  • Yamada, Shinya; Suzuki, Yasuo; Suzuki, Takashi
  • Nature, Vol. 444, Issue 7117
  • DOI: 10.1038/nature05264

Likelihood-enhanced fast translation functions
journal, March 2005

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Storoni, Laurent C.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4
  • DOI: 10.1107/S0907444905001617

Efficient Transmission of Swine‐Adapted but Not Wholly Avian Influenza Viruses among Pigs and from Pigs to Ferrets
journal, December 2009

  • De Vleeschauwer, Annebel; Van Poucke, Sjouke; Braeckmans, Debby
  • The Journal of Infectious Diseases, Vol. 200, Issue 12
  • DOI: 10.1086/648475

Human infections with recently-emerging highly pathogenic H7N9 avian influenza virus in China
journal, July 2017


Use of Influenza Risk Assessment Tool for Prepandemic Preparedness
journal, March 2018

  • Burke, Stephen A.; Trock, Susan C.
  • Emerging Infectious Diseases, Vol. 24, Issue 3
  • DOI: 10.3201/eid2403.171852