Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin

Ni, Fengyun; Kondrashkina, Elena; Wang, Qinghua

doi:10.1371/journal.pone.0134576

Title: Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin

Journal Article · Thu Jul 30 00:00:00 EDT 2015 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0134576· OSTI ID:1498355

Ni, Fengyun ^[1]; Kondrashkina, Elena ^[2]; Wang, Qinghua ^[1]

Baylor College of Medicine, Houston, TX (United States)
Northwestern Univ., Evanston, IL (United States)

In June 2013, the first human infection by avian influenza A(H6N1) virus was reported in Taiwan. This incident raised the concern for possible human epidemics and pandemics from H6 viruses. In this study, we performed structural and functional investigation on the hemagglutinin (HA) proteins of the human-infecting A/Taiwan/2/2013(H6N1) (TW H6) virus and an avian A/chicken/Guangdong/S1311/2010(H6N6) (GD H6) virus that transmitted efficiently in guinea pigs. Our results revealed that in the presence of HA1 Q226, the triad of HA1 S137, E190 and G228 in GD H6 HA allows the binding to both avian- and human-like receptors with a slight preference for avian receptors. Its conservation among the majority of H6 HAs provides an explanation for the broader host range of this subtype. Furthermore, the triad of N137, V190 and S228 in TW H6 HA may alleviate the requirement for a hydrophobic residue at HA₁ 226 of H2 and H3 HAs when binding to human-like receptors. Consequently, TW H6 HA has a slight preference for human receptors, thus may represent an intermediate towards a complete human adaptation. Importantly, the triad observed in TW H6 HA is detected in 74% H6 viruses isolated from Taiwan in the past 14 years, suggesting an elevated threat of H6 viruses from this region to human health. The novel roles of the triad at HA₁ 137, 190 and 228 of H6 HA in binding to receptors revealed here may also be used by other HA subtypes to achieve human adaptation, which needs to be further tested in laboratory and closely monitored in field surveillance.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

OSTI ID:: 1498355

Journal Information:: PLoS ONE, Vol. 10, Issue 7; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 26 works

Citation information provided by
Web of Science

References (61)

Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study Chen, HaiYing; Yuan, Hui; Gao, Rongbao The Lancet, Vol. 383, Issue 9918 https://doi.org/10.1016/S0140-6736(14)60111-2	journal	February 2014
Receptor Binding Properties of the Influenza Virus Hemagglutinin as a Determinant of Host Range Xiong, Xiaoli; McCauley, John W.; Steinhauer, David A. Influenza Pathogenesis and Control - Volume I https://doi.org/10.1007/82_2014_423	book	January 2014
Human infection with avian influenza A H6N1 virus: an epidemiological analysis Wei, Sung-Hsi; Yang, Ji-Rong; Wu, Ho-Sheng The Lancet Respiratory Medicine, Vol. 1, Issue 10 https://doi.org/10.1016/S2213-2600(13)70221-2	journal	December 2013
Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses Byrd-Leotis, L.; Liu, R.; Bradley, K. C. Proceedings of the National Academy of Sciences, Vol. 111, Issue 22 https://doi.org/10.1073/pnas.1323162111	journal	May 2014
Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity Rogers, G. N.; Paulson, J. C.; Daniels, R. S. Nature, Vol. 304, Issue 5921 https://doi.org/10.1038/304076a0	journal	July 1983
An Airborne Transmissible Avian Influenza H5 Hemagglutinin Seen at the Atomic Level Zhang, W.; Shi, Y.; Lu, X. Science, Vol. 340, Issue 6139 https://doi.org/10.1126/science.1236787	journal	May 2013
Origin and molecular characterization of the human-infecting H6N1 influenza virus in Taiwan Shi, Weifeng; Shi, Yi; Wu, Ying Protein & Cell, Vol. 4, Issue 11 https://doi.org/10.1007/s13238-013-3083-0	journal	October 2013
Enabling the 'host jump': structural determinants of receptor-binding specificity in influenza A viruses Shi, Yi; Wu, Ying; Zhang, Wei Nature Reviews Microbiology, Vol. 12, Issue 12 https://doi.org/10.1038/nrmicro3362	journal	November 2014
Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin Skehel, John J.; Wiley, Don C. Annual Review of Biochemistry, Vol. 69, Issue 1 https://doi.org/10.1146/annurev.biochem.69.1.531	journal	June 2000
Receptor determinants of human and animal influenza virus isolates: Differences in receptor specificity of the H3 hemagglutinin based on species of origin Rogers, Gary N.; Paulson, James C. Virology, Vol. 127, Issue 2 https://doi.org/10.1016/0042-6822(83)90150-2	journal	June 1983
The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin Gamblin, S. J. Science, Vol. 303, Issue 5665 https://doi.org/10.1126/science.1093155	journal	March 2004
Specification of Receptor-Binding Phenotypes of Influenza Virus Isolates from Different Hosts Using Synthetic Sialylglycopolymers: Non-Egg-Adapted Human H1 and H3 Influenza A and Influenza B Viruses Share a Common High Binding Affinity for 6′-Sialyl(N-acetyllactosamine) Gambaryan, A. S.; Tuzikov, A. B.; Piskarev, V. E. Virology, Vol. 232, Issue 2 https://doi.org/10.1006/viro.1997.8572	journal	June 1997
Avian influenza A H10N8—a virus on the verge? García-Sastre, Adolfo; Schmolke, Mirco The Lancet, Vol. 383, Issue 9918 https://doi.org/10.1016/s0140-6736(14)60163-x	journal	February 2014
Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega Sievers, Fabian; Wilm, Andreas; Dineen, David Molecular Systems Biology, Vol. 7, Issue 1 https://doi.org/10.1038/msb.2011.75	journal	January 2011
Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957 Liu, J.; Stevens, D. J.; Haire, L. F. Proceedings of the National Academy of Sciences, Vol. 106, Issue 40 https://doi.org/10.1073/pnas.0906849106	journal	September 2009
Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin Lin, Y. P.; Xiong, X.; Wharton, S. A. Proceedings of the National Academy of Sciences, Vol. 109, Issue 52 https://doi.org/10.1073/pnas.1218841110	journal	December 2012
Single-step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides Stemmer, Willem P. C.; Crameri, Andreas; Ha, Kim D. Gene, Vol. 164, Issue 1 https://doi.org/10.1016/0378-1119(95)00511-4	journal	October 1995
The Jalview Java alignment editor Clamp, M.; Cuff, J.; Searle, S. M. Bioinformatics, Vol. 20, Issue 3 https://doi.org/10.1093/bioinformatics/btg430	journal	January 2004
Spatial, Temporal, and Species Variation in Prevalence of Influenza A Viruses in Wild Migratory Birds Munster, Vincent J.; Baas, Chantal; Lexmond, Pascal PLoS Pathogens, Vol. 3, Issue 5 https://doi.org/10.1371/journal.ppat.0030061	journal	January 2007
The CCP4 suite programs for protein crystallography Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/S0907444994003112	journal	September 1994
Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus Tzarum, Netanel; de Vries, Robert P.; Zhu, Xueyong Cell Host & Microbe, Vol. 17, Issue 3 https://doi.org/10.1016/j.chom.2015.02.005	journal	March 2015
Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid Weis, W.; Brown, J. H.; Cusack, S. Nature, Vol. 333, Issue 6172 https://doi.org/10.1038/333426a0	journal	June 1988
Receptor binding by an H7N9 influenza virus from humans Xiong, Xiaoli; Martin, Stephen R.; Haire, Lesley F. Nature, Vol. 499, Issue 7459 https://doi.org/10.1038/nature12372	journal	June 2013
Identification of an H6N6 swine influenza virus in southern China Zhang, Guihong; Kong, Weili; Qi, Wenbao Infection, Genetics and Evolution, Vol. 11, Issue 5 https://doi.org/10.1016/j.meegid.2011.02.023	journal	July 2011
LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery Laskowski, Roman A.; Swindells, Mark B. Journal of Chemical Information and Modeling, Vol. 51, Issue 10 https://doi.org/10.1021/ci200227u	journal	October 2011
Glycan Receptor Binding of the Influenza A Virus H7N9 Hemagglutinin Tharakaraman, Kannan; Jayaraman, Akila; Raman, Rahul Cell, Vol. 153, Issue 7 https://doi.org/10.1016/j.cell.2013.05.034	journal	June 2013
The hemagglutinin structure of an avian H1N1 influenza A virus Lin, Tianwei; Wang, Gengyan; Li, Anzhang Virology, Vol. 392, Issue 1 https://doi.org/10.1016/j.virol.2009.06.028	journal	September 2009
Avian Influenza A Viruses Differ from Human Viruses by Recognition of Sialyloligosaccharides and Gangliosides and by a Higher Conservation of the HA Receptor-Binding Site Matrosovich, M. N.; Gambaryan, A. S.; Teneberg, S. Virology, Vol. 233, Issue 1 https://doi.org/10.1006/viro.1997.8580	journal	June 1997
The Surface Glycoproteins of H5 Influenza Viruses Isolated from Humans, Chickens, and Wild Aquatic Birds Have Distinguishable Properties Matrosovich, Mikhail; Zhou, Nannan; Kawaoka, Yoshihiro Journal of Virology, Vol. 73, Issue 2 https://doi.org/10.1128/JVI.73.2.1146-1155.1999	journal	February 1999
Avian Influenza H6 Viruses Productively Infect and Cause Illness in Mice and Ferrets Gillim-Ross, L.; Santos, C.; Chen, Z. Journal of Virology, Vol. 82, Issue 21 https://doi.org/10.1128/jvi.01206-08	journal	August 2008
Receptor binding properties of human and animal H1 influenza virus isolates Rogers, Gary N.; D'Souza, Bruce L. Virology, Vol. 173, Issue 1 https://doi.org/10.1016/0042-6822(89)90249-3	journal	November 1989
H6 Influenza Viruses Pose a Potential Threat to Human Health Wang, G.; Deng, G.; Shi, J. Journal of Virology, Vol. 88, Issue 8 https://doi.org/10.1128/jvi.03292-13	journal	February 2014
Influenza A Viruses of Migrating Wild Aquatic Birds in North America Krauss, Scott; Walker, David; Pryor, S. Paul Vector-Borne and Zoonotic Diseases, Vol. 4, Issue 3 https://doi.org/10.1089/vbz.2004.4.177	journal	September 2004
Origin and Molecular Characteristics of a Novel 2013 Avian Influenza A(H6N1) Virus Causing Human Infection in Taiwan Yuan, Jian; Zhang, Lei; Kan, Xianzhao Clinical Infectious Diseases, Vol. 57, Issue 9 https://doi.org/10.1093/cid/cit479	journal	November 2013
Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses Nobusawa, E.; Aoyama, T.; Kato, H. Virology, Vol. 182, Issue 2 https://doi.org/10.1016/0042-6822(91)90588-3	journal	June 1991
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses Shi, Y.; Zhang, W.; Wang, F. Science, Vol. 342, Issue 6155 https://doi.org/10.1126/science.1242917	journal	September 2013
Contemporary Avian Influenza A Virus Subtype H1, H6, H7, H10, and H15 Hemagglutinin Genes Encode a Mammalian Virulence Factor Similar to the 1918 Pandemic Virus H1 Hemagglutinin Qi, Li; Pujanauski, Lindsey M.; Davis, A. Sally mBio, Vol. 5, Issue 6 https://doi.org/10.1128/mbio.02116-14	journal	November 2014
Receptor binding by a ferret-transmissible H5 avian influenza virus Xiong, Xiaoli; Coombs, Peter J.; Martin, Stephen R. Nature, Vol. 497, Issue 7449 https://doi.org/10.1038/nature12144	journal	April 2013
Structure and receptor binding preferences of recombinant human A(H3N2) virus hemagglutinins Yang, Hua; Carney, Paul J.; Chang, Jessie C. Virology, Vol. 477 https://doi.org/10.1016/j.virol.2014.12.024	journal	March 2015
Binding of the Influenza A Virus to Cell-Surface Receptors: Structures of Five Hemagglutinin–Sialyloligosaccharide Complexes Determined by X-Ray Crystallography Eisen, Michael B.; Sabesan, Subramaniam; Skehel, John J. Virology, Vol. 232, Issue 1 https://doi.org/10.1006/viro.1997.8526	journal	May 1997
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Structure of the Uncleaved Human H1 Hemagglutinin from the Extinct 1918 Influenza Virus Stevens, J. Science, Vol. 303, Issue 5665 https://doi.org/10.1126/science.1093373	journal	March 2004
Receptor Specificity in Human, Avian, and Equine H2 and H3 Influenza Virus Isolates Connor, Robert J.; Kawaoka, Yoshihiro; Webster, Robert G. Virology, Vol. 205, Issue 1 https://doi.org/10.1006/viro.1994.1615	journal	November 1994
Evidence of Previous Avian Influenza Infection among US Turkey Workers: Avian Influenza in Turkey Workers Kayali, G.; Ortiz, E. J.; Chorazy, M. L. Zoonoses and Public Health, Vol. 57, Issue 4 https://doi.org/10.1111/j.1863-2378.2009.01231.x	journal	April 2009
Experimental infection of dogs with H6N1 avian influenza A virus Cheng, Kaihui; Yu, Zhijun; Gao, Yuwei Archives of Virology, Vol. 159, Issue 9 https://doi.org/10.1007/s00705-014-2058-7	journal	April 2014
A Single Amino Acid Substitution in 1918 Influenza Virus Hemagglutinin Changes Receptor Binding Specificity Glaser, L.; Stevens, J.; Zamarin, D. Journal of Virology, Vol. 79, Issue 17 https://doi.org/10.1128/JVI.79.17.11533-11536.2005	journal	August 2005
Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus Gao, Rongbao; Cao, Bin; Hu, Yunwen New England Journal of Medicine, Vol. 368, Issue 20 https://doi.org/10.1056/NEJMoa1304459	journal	May 2013
A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission Tumpey, T. M.; Maines, T. R.; Van Hoeven, N. Science, Vol. 315, Issue 5812 https://doi.org/10.1126/science.1136212	journal	February 2007
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus Yang, H.; Carney, P. J.; Chang, J. C. Journal of Virology, Vol. 87, Issue 22 https://doi.org/10.1128/JVI.01854-13	journal	September 2013
Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation Nam, J. -H.; Kim, E. -H.; Song, D. Journal of Virology, Vol. 85, Issue 24 https://doi.org/10.1128/jvi.05038-11	journal	October 2011
Structural basis for the divergent evolution of influenza B virus hemagglutinin Ni, Fengyun; Kondrashkina, Elena; Wang, Qinghua Virology, Vol. 446, Issue 1-2 https://doi.org/10.1016/j.virol.2013.07.035	journal	November 2013
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910048675	journal	March 2011
The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases Tang, Terence T. L.; Stowell, James A. W.; Hill, Chris H. Nature Structural & Molecular Biology, Vol. 26, Issue 6 https://doi.org/10.1038/s41594-019-0227-9	journal	May 2019
Structure and Receptor Binding Preferences of Recombinant Hemagglutinins from Avian and Human H6 and H10 Influenza A Virus Subtypes Yang, Hua; Carney, Paul J.; Chang, Jessie C. Journal of Virology, Vol. 89, Issue 8 https://doi.org/10.1128/JVI.03456-14	journal	February 2015
Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. Naeve, C. W.; Hinshaw, V. S.; Webster, R. G. Journal of Virology, Vol. 51, Issue 2 https://doi.org/10.1128/jvi.51.2.567-569.1984	journal	January 1984
The Structure and Function of the Hemagglutinin Membrane Glycoprotein of Influenza Virus Wiley, D. C.; Skehel, J. J. Annual Review of Biochemistry, Vol. 56, Issue 1 https://doi.org/10.1146/annurev.bi.56.070187.002053	journal	June 1987
Differences in sialic acid-galactose linkages in the chicken egg amnion and allantois influence human influenza virus receptor specificity and variant selection. Ito, T.; Suzuki, Y.; Takada, A. Journal of virology, Vol. 71, Issue 4 https://doi.org/10.1128/jvi.71.4.3357-3362.1997	journal	January 1997
Host-mediated selection of influenza virus receptor variants. Sialic acid-alpha 2,6Gal-specific clones of A/duck/Ukraine/1/63 revert to sialic acid-alpha 2,3Gal-specific wild type in ovo. Rogers, G. N.; Daniels, R. S.; Skehel, J. J. Journal of Biological Chemistry, Vol. 260, Issue 12 https://doi.org/10.1016/S0021-9258(17)39617-5	journal	June 1985

Cited By (8)

E190V substitution of H6 hemagglutinin is one of key factors for binding to sulfated sialylated glycan receptor and infection to chickens Kikutani, Yuto; Okamatsu, Masatoshi; Nishihara, Shoko Microbiology and Immunology, Vol. 64, Issue 4 https://doi.org/10.1111/1348-0421.12773	journal	February 2020
Molecular characterization of H6 subtype influenza viruses in southern China from 2009 to 2011 Zou, Shumei; Gao, Rongbao; Zhang, Ye Emerging Microbes & Infections, Vol. 5, Issue 1 https://doi.org/10.1038/emi.2016.71	journal	January 2016
The Drivers of Pathology in Zoonotic Avian Influenza: The Interplay Between Host and Pathogen Horman, William S. J.; Nguyen, Thi H. O.; Kedzierska, Katherine Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.01812	journal	August 2018
Isolation and genetic characterization of novel reassortant H6N6 subtype avian influenza viruses isolated from chickens in eastern China Wu, Haibo; Lu, Rufeng; Peng, Xiuming Archives of Virology, Vol. 161, Issue 7 https://doi.org/10.1007/s00705-016-2861-4	journal	April 2016
Structure basis of neutralization by a novel site II/IV antibody against respiratory syncytial virus fusion protein Xie, Qingqing; Wang, Zhao; Ni, Fengyun PLOS ONE, Vol. 14, Issue 2 https://doi.org/10.1371/journal.pone.0210749	journal	February 2019
Efficacy of a plant‐produced virus‐like particle vaccine in chickens challenged with Influenza A H6N2 virus Smith, Tanja; O'Kennedy, Martha M.; Wandrag, Daniel B. R. Plant Biotechnology Journal, Vol. 18, Issue 2 https://doi.org/10.1111/pbi.13219	journal	August 2019
Isolation and characterization of novel reassortant H6N1 avian influenza viruses from chickens in Eastern China Wu, Haibo; Yang, Fan; Liu, Fumin Virology Journal, Vol. 15, Issue 1 https://doi.org/10.1186/s12985-018-1063-y	journal	October 2018
Continuing evolution of H6N2 influenza a virus in South African chickens and the implications for diagnosis and control Abolnik, Celia; Strydom, Christine; Rauff, Dionne Linda BMC Veterinary Research, Vol. 15, Issue 1 https://doi.org/10.1186/s12917-019-2210-4	journal	December 2019

Similar Records

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

Journal Article · Thu Mar 19 00:00:00 EDT 2015 · Journal of Virology · OSTI ID:1498355

Yang, Hua; Carney, Paul J.; Chang, Jessie C.; +2 more

Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus

Journal Article · Sun Mar 01 00:00:00 EST 2015 · Cell Host & Microbe · OSTI ID:1498355

Tzarum, Netanel; de Vries, Robert P.; Zhu, Xueyong; +4 more

Unique Structural Features of Influenza Virus H15 Hemagglutinin

Journal Article · Wed Apr 12 00:00:00 EDT 2017 · Journal of Virology · OSTI ID:1498355

Tzarum, Netanel; McBride, Ryan; Nycholat, Corwin M.; +4 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Title: Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin

Citation Formats

References (61)

Cited By (8)

Similar Records

Related Subjects