influenza virus hemagglutinin glycoproteins


Summary: Membrane glycoproteins from influenza viruses which are involved in hemagglutination, virus attachment, and envelope fusion. Fourteen distinct subtypes of HA glycoproteins and nine of NA glycoproteins have been identified from INFLUENZA A VIRUS; no subtypes have been identified for Influenza B or Influenza C viruses.

Top Publications

  1. Xu R, McBride R, Paulson J, Basler C, Wilson I. Structure, receptor binding, and antigenicity of influenza virus hemagglutinins from the 1957 H2N2 pandemic. J Virol. 2010;84:1715-21 pubmed publisher
    ..The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine. ..
  2. Zaraket H, Saito R, Sato I, Suzuki Y, Li D, Dapat C, et al. Molecular evolution of human influenza A viruses in a local area during eight influenza epidemics from 2000 to 2007. Arch Virol. 2009;154:285-95 pubmed publisher
    ..Finally, acquisition or loss of N-glycosylation sites was shown to contribute to the evolution of influenza A virus, especially in the case of H3N2, which had a higher tendency to acquire new glycosylation sites. ..
  3. Neumann G, Noda T, Kawaoka Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature. 2009;459:931-9 pubmed publisher
  4. Stevens J, Blixt O, Chen L, Donis R, Paulson J, Wilson I. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. J Mol Biol. 2008;381:1382-94 pubmed publisher
    ..Thus, these avian strains should be considered high-risk, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study. ..
  5. Gambaryan A, Tuzikov A, Pazynina G, Desheva J, Bovin N, Matrosovich M, et al. 6-sulfo sialyl Lewis X is the common receptor determinant recognized by H5, H6, H7 and H9 influenza viruses of terrestrial poultry. Virol J. 2008;5:85 pubmed publisher
    ..These findings suggest that the adaptation to receptors in poultry can enhance the potential of an avian virus for avian-to-human transmission and pandemic spread. ..
  6. Nolan T, Richmond P, Skeljo M, Pearce G, Hartel G, Formica N, et al. Phase I and II randomised trials of the safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in healthy adults. Vaccine. 2008;26:4160-7 pubmed publisher
    ..The prototype H5N1 vaccine also elicited modest levels of cross-protective MN antibodies against variant clade 2 H5N1 strains [ identifiers: NCT00136331, NCT00320346; CSL Limited, Australia]. ..
  7. DiNapoli J, Nayak B, Yang L, Finneyfrock B, Cook A, Andersen H, et al. Newcastle disease virus-vectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys. J Virol. 2010;84:1489-503 pubmed publisher
    ..The study also identified NA as an independent protective HPAIV antigen in primates. Furthermore, we demonstrated the feasibility of aerosol delivery of NDV-vectored vaccines. ..
  8. Wang C, Chen J, Tseng Y, Hsu C, Hung Y, Chen S, et al. Glycans on influenza hemagglutinin affect receptor binding and immune response. Proc Natl Acad Sci U S A. 2009;106:18137-42 pubmed publisher
    ..Thus, removal of structurally nonessential glycans on viral surface glycoproteins may be a very effective and general approach for vaccine design against influenza and other human viruses...
  9. Garten R, Davis C, Russell C, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197-201 pubmed publisher
    ..Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1)...

More Information


  1. Chiu F, Venkatesan N, Wu C, Chou A, Chen H, Lian S, et al. Immunological study of HA1 domain of hemagglutinin of influenza H5N1 virus. Biochem Biophys Res Commun. 2009;383:27-31 pubmed publisher
  2. Kreijtz J, Suezer Y, de Mutsert G, van den Brand J, van Amerongen G, Schnierle B, et al. Preclinical evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine against influenza A/H5N1 viruses. Vaccine. 2009;27:6296-9 pubmed publisher
    ..Therefore MVA-HA-VN/04 is a promising vaccine candidate for the induction of protective immunity against highly pathogenic avian influenza A/H5N1 viruses. ..
  3. Rambaut A, Pybus O, Nelson M, Viboud C, Taubenberger J, Holmes E. The genomic and epidemiological dynamics of human influenza A virus. Nature. 2008;453:615-9 pubmed publisher
    ..These results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions. ..
  4. Takahashi T, Hashimoto A, Maruyama M, Ishida H, Kiso M, Kawaoka Y, et al. Identification of amino acid residues of influenza A virus H3 HA contributing to the recognition of molecular species of sialic acid. FEBS Lett. 2009;583:3171-4 pubmed publisher
    ..We evaluated the binding ability with four types of synthetic sialylglycolipids. The results indicate that the amino acid substitutions Thr155 to Tyr and Glu158 to Gly in H3 HA facilitate virus binding to N-glycolylneuraminic acid. ..
  5. Bhattacharya P, Grimme S, Ganesh B, Gopisetty A, Sheng J, Martinez O, et al. Nanodisc-incorporated hemagglutinin provides protective immunity against influenza virus infection. J Virol. 2010;84:361-71 pubmed publisher
    ..HA-ND vaccination conferred protection that was comparable to that of Fluzone and FluMist against challenge with influenza virus strain A/Puerto Rico/8/1934 (H1N1). ..
  6. Sui J, Hwang W, Perez S, Wei G, Aird D, Chen L, et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009;16:265-73 pubmed publisher
    ..Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses. ..
  7. Van Hoeven N, Pappas C, Belser J, Maines T, Zeng H, Garcia Sastre A, et al. Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air. Proc Natl Acad Sci U S A. 2009;106:3366-71 pubmed publisher
    ..These findings demonstrate that the adaptation of the HA and PB2 proteins are critical for the development of pandemic influenza strains from avian influenza viruses. ..
  8. Steel J, Lowen A, Pena L, Angel M, Solórzano A, Albrecht R, et al. Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J Virol. 2009;83:1742-53 pubmed publisher
  9. Pavlova S, Veits J, Keil G, Mettenleiter T, Fuchs W. Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase. Vaccine. 2009;27:773-85 pubmed publisher
    ..Furthermore, chickens vaccinated with ILTV vectors can be easily differentiated from influenza virus-infected animals by the absence of serum antibodies against the AIV nucleoprotein. ..
  10. Shen S, Mahadevappa G, Oh H, Wee B, Choi Y, Hwang L, et al. Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza A (H5N1) virus expressed in insect cells and bacteria. J Med Virol. 2008;80:1972-83 pubmed publisher
    ..Using a novel membrane fusion assay, the abilities of these antibodies to block membrane fusion were found to correlate well with the neutralization activities. ..
  11. Kasson P, Pande V. Structural basis for influence of viral glycans on ligand binding by influenza hemagglutinin. Biophys J. 2008;95:L48-50 pubmed publisher
    ..We also predict that the proximity of these interactions to the ligand-binding pocket will impact the binding affinity of small glycomimetic ligands analogous to the influenza neuraminidase inhibitors currently in clinical use. ..
  12. Kongchanagul A, Suptawiwat O, Kanrai P, Uiprasertkul M, Puthavathana P, Auewarakul P. Positive selection at the receptor-binding site of haemagglutinin H5 in viral sequences derived from human tissues. J Gen Virol. 2008;89:1805-10 pubmed publisher
    ..Our data provide new candidate mutations for the viral adaptation to a human host, and a new approach to search for new genetic markers of potential pandemic viruses. ..
  13. De Groot A, Ardito M, McClaine E, Moise L, Martin W. Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine. Vaccine. 2009;27:5740-7 pubmed publisher
  14. Russell C, Jones T, Barr I, Cox N, Garten R, Gregory V, et al. The global circulation of seasonal influenza A (H3N2) viruses. Science. 2008;320:340-6 pubmed publisher
  15. Kashyap A, Steel J, Oner A, Dillon M, Swale R, Wall K, et al. Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies. Proc Natl Acad Sci U S A. 2008;105:5986-91 pubmed publisher
    ..Remarkably, three of these antibodies neutralized both H1 and H5 subtype influenza viruses. ..
  16. Qi L, Kash J, Dugan V, Wang R, Jin G, Cunningham R, et al. Role of sialic acid binding specificity of the 1918 influenza virus hemagglutinin protein in virulence and pathogenesis for mice. J Virol. 2009;83:3754-61 pubmed publisher
    ..Changing alpha2-3 to alpha2-6 binding specificity did not increase the lethality of an avian-adapted hemagglutinin. Thus, the 1918 hemagglutinin contains murine virulence determinants independent of receptor binding specificity. ..
  17. Maines T, Jayaraman A, Belser J, Wadford D, Pappas C, Zeng H, et al. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science. 2009;325:484-7 pubmed publisher
  18. Throsby M, van den Brink E, Jongeneelen M, Poon L, Alard P, Cornelissen L, et al. Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS ONE. 2008;3:e3942 pubmed publisher
    ..Finally our approach of screening the IgM(+) memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. ..
  19. Wei C, Xu L, Kong W, Shi W, Canis K, Stevens J, et al. Comparative efficacy of neutralizing antibodies elicited by recombinant hemagglutinin proteins from avian H5N1 influenza virus. J Virol. 2008;82:6200-8 pubmed publisher
    ..Taken together, these results suggest that recombinant HA proteins as individual or oligomeric trimers can elicit potent neutralizing antibody responses to avian H5N1 influenza viruses. ..
  20. Shen J, Kirk B, Ma J, Wang Q. Diversifying selective pressure on influenza B virus hemagglutinin. J Med Virol. 2009;81:114-24 pubmed publisher
    ..Thus, any newly emerging strains need to be placed in the context of their evolutionary history in order to understand and predict their epidemic potential. ..
  21. Shi W, Gibbs M, Zhang Y, Zhuang D, Dun A, Yu G, et al. The variable codons of H5N1 avian influenza A virus haemagglutinin genes. Sci China C Life Sci. 2008;51:987-93 pubmed publisher
    ..Although the functions of some positively selected positions are unknown, our analysis provided evidence of different temporal, spatial and host adaptations for H5N1 avian influenza viruses. ..
  22. Liu J, Stevens D, Haire L, Walker P, Coombs P, Russell R, et al. Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957. Proc Natl Acad Sci U S A. 2009;106:17175-80 pubmed publisher
    ..We consider the significance for the development of pandemics, of the existence of avian viruses that can bind to both avian and human receptors. ..
  23. Biesova Z, Miller M, Schneerson R, Shiloach J, Green K, Robbins J, et al. Preparation, characterization, and immunogenicity in mice of a recombinant influenza H5 hemagglutinin vaccine against the avian H5N1 A/Vietnam/1203/2004 influenza virus. Vaccine. 2009;27:6234-8 pubmed publisher
    ..Using this method, rHA vaccine can be produced in 3-4 weeks and when formulated with alum, induces HA antibody levels in young outbred mice consistent with the FDA guidelines for vaccines against epidemic and pandemic influenza. ..
  24. Ellebedy A, Webby R. Influenza vaccines. Vaccine. 2009;27 Suppl 4:D65-8 pubmed publisher
    ..Within the context of biodefense, the issue will be to reach a balance where some of the diversity of influenza viruses can be encompassed within a vaccine while maintaining an acceptable level of efficacy. ..
  25. Bateman A, Busch M, Karasin A, Bovin N, Olsen C. Amino acid 226 in the hemagglutinin of H4N6 influenza virus determines binding affinity for alpha2,6-linked sialic acid and infectivity levels in primary swine and human respiratory epithelial cells. J Virol. 2008;82:8204-9 pubmed publisher
    ..Using specific neuraminidases, we found that irrespective of their relative binding preferences, all of the influenza viruses examined utilized SAalpha2,6Gal to infect swine and human cells. ..
  26. Mayrhofer J, Coulibaly S, Hessel A, Holzer G, Schwendinger M, Brühl P, et al. Nonreplicating vaccinia virus vectors expressing the H5 influenza virus hemagglutinin produced in modified Vero cells induce robust protection. J Virol. 2009;83:5192-203 pubmed publisher
    ..Thus, the nonreplicating recombinant vaccinia virus vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system. ..
  27. Stech O, Veits J, Weber S, Deckers D, Schröer D, Vahlenkamp T, et al. Acquisition of a polybasic hemagglutinin cleavage site by a low-pathogenic avian influenza virus is not sufficient for immediate transformation into a highly pathogenic strain. J Virol. 2009;83:5864-8 pubmed publisher
  28. Ekiert D, Bhabha G, Elsliger M, Friesen R, Jongeneelen M, Throsby M, et al. Antibody recognition of a highly conserved influenza virus epitope. Science. 2009;324:246-51 pubmed publisher
    ..The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza. ..
  29. Pfeiffer J, Pantin Jackwood M, To T, Nguyen T, Suarez D. Phylogenetic and biological characterization of highly pathogenic H5N1 avian influenza viruses (Vietnam 2005) in chickens and ducks. Virus Res. 2009;142:108-20 pubmed publisher
    ..The information gained about these viruses provides insight with regards to implementing control programs, including vaccine seed strain selection. ..
  30. Matsuoka Y, Swayne D, Thomas C, Rameix Welti M, Naffakh N, Warnes C, et al. Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J Virol. 2009;83:4704-8 pubmed publisher
    ..The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans...
  31. Yen H, Aldridge J, Boon A, Ilyushina N, Salomon R, Hulse Post D, et al. Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread. Proc Natl Acad Sci U S A. 2009;106:286-91 pubmed publisher
    ..These results show that VN1203 HA glycoprotein confers pathogenicity by facilitating systemic spread in mice; they also suggest that a minor change in receptor binding domain may modulate the virulence of H5N1 viruses. ..
  32. Stech J, Stech O, Herwig A, Altmeppen H, Hundt J, Gohrbandt S, et al. Rapid and reliable universal cloning of influenza A virus genes by target-primed plasmid amplification. Nucleic Acids Res. 2008;36:e139 pubmed publisher
    ..In case the PCR amplicon ends are homologous to the plasmid annealing sites only, this method is suitable for cloning of any insert with conserved termini. ..
  33. Igarashi M, Ito K, Kida H, Takada A. Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin. Virology. 2008;376:323-9 pubmed publisher
    ..We hypothesize that influenza viruses maintained in natural reservoirs could have different potentials for sustained circulation, depending on their HA subtypes, if introduced into the human population. ..
  34. Hofmann M, Renzullo S, Baumer A. Phylogenetic characterization of H5N1 highly pathogenic avian influenza viruses isolated in Switzerland in 2006. Virus Genes. 2008;37:407-13 pubmed publisher
    ..Phylogenetic analysis revealed that all the virus isolates were highly similar to each other and to other H5N1 strains found in neighboring countries. All analyzed Swiss virus isolates belonged to the influenza virus subclade 2.2.1. ..
  35. Suguitan A, Marino M, Desai P, Chen L, Matsuoka Y, Donis R, et al. The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus. Virology. 2009;395:280-8 pubmed publisher
  36. Gao Y, Zhang Y, Shinya K, Deng G, Jiang Y, Li Z, et al. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog. 2009;5:e1000709 pubmed publisher
    ..These amino acids changes in PB2 and HA could serve as important molecular markers for assessing the pandemic potential of H5N1 field isolates. ..
  37. Zhang Y, Lin X, Zhang F, Wu J, Tan W, Bi S, et al. Hemagglutinin and neuraminidase matching patterns of two influenza A virus strains related to the 1918 and 2009 global pandemics. Biochem Biophys Res Commun. 2009;387:405-8 pubmed publisher
    ..Our study demonstrated that some reassortments of H1N1 viruses may hold the potential to produce higher infectivity than do their ancestors. ..
  38. Wu Q, Fang L, Wu X, Li B, Luo R, Yu Z, et al. A pseudotype baculovirus-mediated vaccine confers protective immunity against lethal challenge with H5N1 avian influenza virus in mice and chickens. Mol Immunol. 2009;46:2210-7 pubmed publisher
    ..These data indicate that the pseudotype baculovirus-mediated vaccine could be utilized as an alternative strategy against the pandemic spread of H5N1 influenza virus. ..
  39. Russell R, Kerry P, Stevens D, Steinhauer D, Martin S, Gamblin S, et al. Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion. Proc Natl Acad Sci U S A. 2008;105:17736-41 pubmed publisher
    ..The nature of the binding site suggests routes for the chemical modification of TBHQ that could lead to the development of more potent inhibitors of membrane fusion and potential anti-influenza drugs. ..
  40. Nicholls J, Chan R, Russell R, Air G, Peiris J. Evolving complexities of influenza virus and its receptors. Trends Microbiol. 2008;16:149-57 pubmed publisher
    ..Understanding these additional components is important in comprehending the infection and the transmission of both existing human influenza viruses and newly emerging avian influenza viruses. ..
  41. Srinivasan A, Viswanathan K, Raman R, Chandrasekaran A, Raguram S, Tumpey T, et al. Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses. Proc Natl Acad Sci U S A. 2008;105:2800-5 pubmed publisher
    ..In summary, this study establishes a quantitative biochemical correlate for influenza A virus transmission. ..
  42. Wang G, Zhan D, Li L, Lei F, Liu B, Liu D, et al. H5N1 avian influenza re-emergence of Lake Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation. J Gen Virol. 2008;89:697-702 pubmed publisher
    ..These findings implicate that QH06 viruses of Lake Qinghai may travel back via migratory birds, though not ruling out the possibility of local circulation of viruses of Lake Qinghai. ..
  43. Bright R, Carter D, Crevar C, Toapanta F, Steckbeck J, Cole K, et al. Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle. PLoS ONE. 2008;3:e1501 pubmed publisher
  44. Plonsky I, Kingsley D, Rashtian A, Blank P, Zimmerberg J. Initial size and dynamics of viral fusion pores are a function of the fusion protein mediating membrane fusion. Biol Cell. 2008;100:377-86 pubmed publisher
    ..The structure of the initial fusion pore detected by electrical conductance measurements is sensitive to the nature of the fusion protein. ..
  45. Du X, Wang Z, Wu A, Song L, Cao Y, Hang H, et al. Networks of genomic co-occurrence capture characteristics of human influenza A (H3N2) evolution. Genome Res. 2008;18:178-87 pubmed
  46. Nicholls J, Bourne A, Chen H, Guan Y, Peiris J. Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses. Respir Res. 2007;8:73 pubmed
    ..This finding is important if conclusions about the potential binding sites of SAalpha2,3 binding viruses, such as influenza or human parainfluenza are to be made. ..
  47. Lee M, Chen M, Liao Y, Hsiung C. Identifying potential immunodominant positions and predicting antigenic variants of influenza A/H3N2 viruses. Vaccine. 2007;25:8133-9 pubmed
    ..The model could be readily integrated to the global influenza surveillance system. ..
  48. Thoennes S, Li Z, Lee B, Langley W, Skehel J, Russell R, et al. Analysis of residues near the fusion peptide in the influenza hemagglutinin structure for roles in triggering membrane fusion. Virology. 2008;370:403-14 pubmed
    ..3 relative to WT. The results are discussed in relation to possible mechanisms by which HA structural rearrangements are initiated at low pH and clade-specific differences near the fusion peptide. ..
  49. Pappas C, Matsuoka Y, Swayne D, Donis R. Development and evaluation of an Influenza virus subtype H7N2 vaccine candidate for pandemic preparedness. Clin Vaccine Immunol. 2007;14:1425-32 pubmed
    ..These studies indicate that H7N2-PR8 is immunogenic, safe, and protective in animal models; these are the essential attributes to qualify for phase I human clinical trials as a prepandemic vaccine. ..
  50. Kaverin N, Rudneva I, Govorkova E, Timofeeva T, Shilov A, Kochergin Nikitsky K, et al. Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies. J Virol. 2007;81:12911-7 pubmed
  51. Yang Z, Wei C, Kong W, Wu L, Xu L, Smith D, et al. Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science. 2007;317:825-8 pubmed
    ..Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains. ..
  52. Yassine H, Lee C, Suarez D, Saif Y. Genetic and antigenic relatedness of H3 subtype influenza A viruses isolated from avian and mammalian species. Vaccine. 2008;26:966-77 pubmed publisher
    ..This also emphasizes the importance of using viruses for vaccines that are antigenically similar to the field strains. ..
  53. Auewarakul P, Suptawiwat O, Kongchanagul A, Sangma C, Suzuki Y, Ungchusak K, et al. An avian influenza H5N1 virus that binds to a human-type receptor. J Virol. 2007;81:9950-5 pubmed
    ..Our data confirm the presence of H5N1 virus with the ability to bind to a human-type receptor in this patient and suggest the selection and expansion of the mutant with human-type receptor specificity in the human host environment. ..