Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses

Abstract

During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015, the virus was detected in wild birds in Canada and the United States, and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North American lineages. In particular, viruses were found with N1, N2, and N8 neuraminidase vRNAs, and these are collectively referred to as H5Nx viruses. In the United States, more than 48 million domestic birds have been affected. Here we present a detailed structural and biochemical analysis of the surface antigens of H5N1, H5N2, and H5N8 viruses in addition to those of a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA-approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses and to continually assess future changes that may increase their pandemic potential. The H5Nx viruses emerging in North America, Europe, and Asia pose a great public health concern. Here we report a molecularmore » and structural study of the major surface proteins of several H5Nx influenza viruses. Furthermore, our results improve the understanding of these new viruses and provide important information on their receptor preferences and susceptibilities to antivirals, which are central to pandemic risk assessment.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2]
+ Show Author Affiliations
  1. Centers for Disease Control and Prevention, Atlanta, GA (United States)
  2. St. Jude Children's Research Hospital, Knoxville, TN (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of General Medical Sciences; HHS; Center for Disease Control and Prevention (CDC)
OSTI Identifier:
1257478
Grant/Contract Number:  
AC02-06CH11357; GM62116
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 90; Journal Issue: 12; Journal ID: ISSN 0022-538X
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Yang, Hua, Carney, Paul J., Mishin, Vasiliy P., Guo, Zhu, Chang, Jessie C., Wentworth, David E., Gubareva, Larisa V., Stevens, James, and Schultz-Cherry, S. Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses. United States: N. p., 2016. Web. doi:10.1128/JVI.00180-16.
Copy to clipboard
Yang, Hua, Carney, Paul J., Mishin, Vasiliy P., Guo, Zhu, Chang, Jessie C., Wentworth, David E., Gubareva, Larisa V., Stevens, James, & Schultz-Cherry, S. Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses. United States. https://doi.org/10.1128/JVI.00180-16
Copy to clipboard
Yang, Hua, Carney, Paul J., Mishin, Vasiliy P., Guo, Zhu, Chang, Jessie C., Wentworth, David E., Gubareva, Larisa V., Stevens, James, and Schultz-Cherry, S. Fri . "Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses". United States. https://doi.org/10.1128/JVI.00180-16. https://www.osti.gov/servlets/purl/1257478.
Copy to clipboard
@article{osti_1257478,
title = {Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses},
author = {Yang, Hua and Carney, Paul J. and Mishin, Vasiliy P. and Guo, Zhu and Chang, Jessie C. and Wentworth, David E. and Gubareva, Larisa V. and Stevens, James and Schultz-Cherry, S.},
abstractNote = {During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015, the virus was detected in wild birds in Canada and the United States, and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North American lineages. In particular, viruses were found with N1, N2, and N8 neuraminidase vRNAs, and these are collectively referred to as H5Nx viruses. In the United States, more than 48 million domestic birds have been affected. Here we present a detailed structural and biochemical analysis of the surface antigens of H5N1, H5N2, and H5N8 viruses in addition to those of a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA-approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses and to continually assess future changes that may increase their pandemic potential. The H5Nx viruses emerging in North America, Europe, and Asia pose a great public health concern. Here we report a molecular and structural study of the major surface proteins of several H5Nx influenza viruses. Furthermore, our results improve the understanding of these new viruses and provide important information on their receptor preferences and susceptibilities to antivirals, which are central to pandemic risk assessment.},
doi = {10.1128/JVI.00180-16},
journal = {Journal of Virology},
number = 12,
volume = 90,
place = {United States},
year = {Fri May 27 00:00:00 EDT 2016},
month = {Fri May 27 00:00:00 EDT 2016}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1128/JVI.00180-16
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 47 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Influenza neuraminidase: Influenza neuraminidase
journal, November 2011

Evidence for a sialosyl cation transition-state complex in the reaction of sialidase from influenza virus
journal, July 1992

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

Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site
journal, September 2012

  • Zhu, Xueyong; Yang, Hua; Guo, Zhu
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 46
  • DOI: 10.1073/pnas.1212579109

Immunization by Avian H5 Influenza Hemagglutinin Mutants with Altered Receptor Binding Specificity
journal, August 2007

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

Host cell proteases controlling virus pathogenicity
journal, February 1994

Influenza A Virus N5 Neuraminidase Has an Extended 150-Cavity
journal, June 2011

Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity
journal, July 1983

  • Rogers, G. N.; Paulson, J. C.; Daniels, R. S.
  • Nature, Vol. 304, Issue 5921
  • DOI: 10.1038/304076a0

Evolution and ecology of influenza A viruses.
journal, January 1992

Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic
journal, June 2006

  • Neumann, Gabriele; Kawaoka, Yoshihiro
  • Emerging Infectious Diseases, Vol. 12, Issue 6
  • DOI: 10.3201/eid1206.051336

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

Nomenclature updates resulting from the evolution of avian influenza A(H5) virus clades 2.1.3.2a, 2.2.1, and 2.3.4 during 2013-2014
journal, August 2015

  • Smith, Gavin J. D.; Donis, Ruben O.
  • Influenza and Other Respiratory Viruses, Vol. 9, Issue 5
  • DOI: 10.1111/irv.12324

The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin
journal, March 2004

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design
journal, August 2006

  • Russell, Rupert J.; Haire, Lesley F.; Stevens, David J.
  • Nature, Vol. 443, Issue 7107
  • DOI: 10.1038/nature05114

Structural Characterization of the 1918 Influenza Virus H1N1 Neuraminidase
journal, August 2008

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

Structure of Influenza Virus N7: the Last Piece of the Neuraminidase "Jigsaw" Puzzle
journal, June 2014

The Potential for Respiratory Droplet-Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host
journal, June 2012

New World Bats Harbor Diverse Influenza A Viruses
journal, October 2013

Novel Eurasian Highly Pathogenic Avian Influenza A H5 Viruses in Wild Birds, Washington, USA, 2014
journal, May 2015

  • Ip, Hon S.; Torchetti, Mia Kim; Crespo, Rocio
  • Emerging Infectious Diseases, Vol. 21, Issue 5
  • DOI: 10.3201/eid2105.142020

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

The VASP tetramerization domain is a right-handed coiled coil based on a 15-residue repeat
journal, November 2004

  • Kuhnel, K.; Jarchau, T.; Wolf, E.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 49
  • DOI: 10.1073/pnas.0403069101

The Amino Acid at the X Position of an Asn-X-Ser Sequon Is an Important Determinant of N-Linked Core-glycosylation Efficiency
journal, March 1996

  • Shakin-Eshleman, Susan H.; Spitalnik, Steven L.; Kasturi, Lakshmi
  • Journal of Biological Chemistry, Vol. 271, Issue 11
  • DOI: 10.1074/jbc.271.11.6363

The CCP4 suite programs for protein crystallography
journal, September 1994

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

Calcium is needed for the thermostability of influenza B virus neuraminidase
journal, February 1994

Three-dimensional structure of neuraminidase of subtype N9 from an avian influenza virus
journal, January 1987

  • Baker, A. T.; Varghese, J. N.; Laver, W. G.
  • Proteins: Structure, Function, and Genetics, Vol. 2, Issue 2
  • DOI: 10.1002/prot.340020205

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

Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding.
journal, January 1995

The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid.
journal, January 1992

Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion
journal, November 2008

  • Russell, R. J.; Kerry, P. S.; Stevens, D. J.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 46
  • DOI: 10.1073/pnas.0807142105

H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes
journal, August 2004

Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus
journal, February 1998

Structural and Antigenic Variation among Diverse Clade 2 H5N1 Viruses
journal, September 2013

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

Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferyl-α-d-N-acetylneuraminate) substrate
journal, April 1979

Structural and Functional Analysis of Surface Proteins from an A(H3N8) Influenza Virus Isolated from New England Harbor Seals
journal, December 2014

  • Yang, Hua; Nguyen, Ha T.; Carney, Paul J.
  • Journal of Virology, Vol. 89, Issue 5
  • DOI: 10.1128/JVI.02723-14

Human infection with a novel, highly pathogenic avian influenza A (H5N6) virus: Virological and clinical findings
journal, January 2016

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

Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution
journal, May 1983

  • Varghese, J. N.; Laver, W. G.; Colman, P. M.
  • Nature, Vol. 303, Issue 5912
  • DOI: 10.1038/303035a0

Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957
journal, September 2009

  • Liu, J.; Stevens, D. J.; Haire, L. F.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 40
  • DOI: 10.1073/pnas.0906849106

Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution
journal, January 1981

  • Wilson, I. A.; Skehel, J. J.; Wiley, D. C.
  • Nature, Vol. 289, Issue 5796
  • DOI: 10.1038/289366a0

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

Glycan Microarray Analysis of the Hemagglutinins from Modern and Pandemic Influenza Viruses Reveals Different Receptor Specificities
journal, February 2006

The neuraminidase of influenza virus
journal, January 1989

  • Air, Gillian M.; Laver, W. Graeme
  • Proteins: Structure, Function, and Genetics, Vol. 6, Issue 4
  • DOI: 10.1002/prot.340060402

Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses
journal, September 2008

Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus
journal, March 2006

Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia
journal, July 2005

  • Hulse-Post, D. J.; Sturm-Ramirez, K. M.; Humberd, J.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 30
  • DOI: 10.1073/pnas.0504662102

X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs
journal, September 2001

  • Ha, Y.; Stevens, D. J.; Skehel, J. J.
  • Proceedings of the National Academy of Sciences, Vol. 98, Issue 20
  • DOI: 10.1073/pnas.201401198

The antigenic architecture of the hemagglutinin of influenza H5N1 viruses
journal, December 2013

[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997

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

Structure and Receptor Binding Specificity of Hemagglutinin H13 from Avian Influenza A Virus H13N6
journal, June 2013

Evolution and ecology of influenza A viruses
journal, March 1992

Structure and Receptor binding properties of a pandemic H1N1 virus hemagglutinin
journal, March 2010

Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021

Influenza Neuraminidase
journal, May 2009

MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
text, January 2007

  • B., Chen, Vincent; C., Richardson, David; S., Richardson, Jane
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/m2an-p252

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

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.45787
    Sort by:
    [ × clear filter / sort ]

    Works referencing / citing this record:

    Selective detections of single-viruses using solid-state nanopores
    journal, November 2018

    Structure of an Influenza A virus N9 neuraminidase with a tetrabrachion-domain stalk
    journal, January 2019

    • Streltsov, Victor A.; Schmidt, Peter M.; McKimm-Breschkin, Jennifer L.
    • Acta Crystallographica Section F Structural Biology Communications, Vol. 75, Issue 2
    • DOI: 10.1107/s2053230x18017892

    A study of the relationship between human infection with avian influenza a (H5N6) and environmental avian influenza viruses in Fujian, China
    journal, September 2019

    Full sequence analysis of hemagglutinin and neuraminidase genes and proteins of highly pathogenic avian influenza H5N1 virus detected in Iran, 2015
    journal, October 2018

    • Yegani, Sima; Shoushtari, Abdel-Hamid; Eshratabadi, Fatemeh
    • Tropical Animal Health and Production, Vol. 51, Issue 3
    • DOI: 10.1007/s11250-018-1731-3

    Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models
    journal, September 2017

    Metabolic machinery encrypted in the Raman spectrum of influenza A virus‐inoculated mammalian cells
    journal, November 2019

    • Pezzotti, Giuseppe; Zhu, Wenliang; Adachi, Tetsuya
    • Journal of Cellular Physiology, Vol. 235, Issue 6
    • DOI: 10.1002/jcp.29392

    The Emergence and Decennary Distribution of Clade 2.3.4.4 HPAI H5Nx
    journal, May 2019

    Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
    journal, January 2018

    Identification of antigenic epitopes in the haemagglutinin protein of H7 avian influenza virus
    journal, October 2019

      Sort by:
      [ × clear filter / sort ]

      Similar Records in DOE PAGES and OSTI.GOV collections: