Influenza pp 33-56 | Cite as

Viral Structure and Composition

  • Edwin D. Kilbourne


The influenza viruses comprise three types of viruses that are closely related in structure, chemical composition, and biological activity. These viruses, types A, B, and C, are pleomorphic enveloped viruses bearing surface projections (peplomers or spikes). Influenza A and B viruses contain four major structural proteins and three proteins with RNA replicase and transcriptase activity (Table 3–1). Eight segments of linear, single-stranded RNA are contained in separate nucleocapsids—rodlike structures of nucleoprotein (NP) (Heggeness et al., 1982)— with which the replicase and transcriptase proteins PB1, PB2, and PA are in close association in an RNP complex. The interior of the virus particle is delimited by repeating units of the matrix or membrane (M) protein in all three viral subtypes. The external spikes of influenza A and B viruses number 400 to 500 (Ruigrok et al., 1984) and comprise two different glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). In the case of influenza C virus, only seven RNA segments and a single external glycoprotein have been demonstrated.


Influenza Virus Virus Particle Glycosylation Site Viral Membrane Carbohydrate Side Chain 
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  1. Air, G. M., and Compans, R. W., 1983, Influenza B and influenza C viruses, in: Genetics of Influenza Viruses (P. Palese and D. W. Kingsbury, eds.), Springer-Verlag, New York, pp. 280–304.Google Scholar
  2. Allen, A. K., Skehel, J. J., and Yuferov, V., 1977, The amino acid and carbohydrate composition of the neuraminidase of B/Lee/40 influenza virus, J. Gen. Virol 37:625–628.Google Scholar
  3. Apostolov, K., and Flewett, T. H., 1969, Further observations on the structure of influenza viruses A and C, J. Gen. Virol. 4:365–370.PubMedGoogle Scholar
  4. Blok, J., Air, G. M., Laver, W. G., et al., 1982, Studies on the size, chemical composition, and partial sequence of the neuraminidase (NA) from type A influenza viruses show that the N-terminal region of the NA is not processed and serves to anchor the NA in the viral membrane, Virology 119:109–121.PubMedGoogle Scholar
  5. Blough, H. A., 1963, The effect of vitamin A alcohol on the morphology of myxoviruses. I. The production and comparison of artificially produced filamentous virus, Virology 19:349–358.PubMedGoogle Scholar
  6. Blough, H. A., and Lawson, D. E. M., 1968, The lipids of paramyxoviruses: A comparative study of Sendai and Newcastle disease viruses, Virology 36:286–292.PubMedGoogle Scholar
  7. Brown, L. E., Ward, C. W., and Jackson, D. C., 1982, Antigenic determinants of influenza virus hemagglutinin-IX. The carbohydrate side chains from an Asian strain, Mol. Immunol. 19:329–338.PubMedGoogle Scholar
  8. Bucher, D. L., and Kilbourne, E. D., 1972, A (N2) neuraminidase of the X-7 influenza virus recombinant: Determination of molecular size and subunit composition of the active unit, J.. Virol. 10:60–66.PubMedGoogle Scholar
  9. Caton, A. J., Brownlee, G. G., Yewdell, J. W., et al., 1982, The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (HI subtype), Cell 31:417–427.PubMedGoogle Scholar
  10. Choppin, P. W., and Compans, R. W., 1975, The structure of influenza virus, in: The Influenza Virus and Influenza (E. D. Kilbourne, ed.), Academic Press, New York, pp. 15–47.Google Scholar
  11. Choppin, P. W., Murphy, J. S., and Tamm, I., 1960, Studies of two kinds of virus particles which comprise influenza A2 virus strains. III. Morphological characteristics: Independence of morphological and functional traits,J.. Exp. Med. 112:945–952.PubMedGoogle Scholar
  12. Choppin, P. W., Murphy, J. S., and Stoeckenius, W., 1961, Surface structure of influenza virus filaments, Virology 13:548–550.PubMedGoogle Scholar
  13. Clerx, J. P. M., Fuller, F., and Bishop, D. H. L., 1983, Tick-borne viruses structurally similar to orthomyxoviruses, Virology 127:205–219.PubMedGoogle Scholar
  14. Colman, P. M., and Ward, C. W., 1985, Structure and diversity of the influenza virus neuraminidase, Curr. Top. Microbiol. Immunol. 114:177–225.PubMedGoogle Scholar
  15. Colman, P. M., Varghese, J. N., and Laver, W. G., 1983, Structure of the catalytic and antigenic sites in influenza virus neuraminidase, Nature 303:41–44.PubMedGoogle Scholar
  16. Compans, R. W., Dimmock, N. J., and Meier-Ewert, H., 1969, Effect of antibody to neuraminidase on the maturation and hemagglutinating activity of an influenza A virus, J.. Virol. 4:528–534.PubMedGoogle Scholar
  17. Compans, R. W., Content, J., and Duesberg, P. H., 1972, Structure of the ribonucleoprotein of influenza virus, J. Virol. 10:795–800.PubMedGoogle Scholar
  18. Cusack, S., Ruigrok, R. W. H., Krygsman, P. C. J., et al, 1985, Structure and composition of influenza virus. A small-angle neutron scattering study, J.. Mol. Biol. 186:565–582.PubMedGoogle Scholar
  19. Desselberger, U., Racaniello, V. R., Zazra, J. J., et al., 1980, The 3 and 5-terminal sequences of influenza A, B and C virus RNA segments are highly conserved and show partial inverted complementarity, Gene 8:315–328.PubMedGoogle Scholar
  20. Erickson, A. H., 1977, Different trypsin sensitivity of the hemagglutinin from antigenically similar recombinant influenza viruses ,doctoral dissertation. Department of Microbiology, Mount Sinai School of Medicine, Graduate School of Biological Sciences, The City University of New York, New York.Google Scholar
  21. Erickson, A. H., and Kilbourne, E. D., 1980, Mutation in the hemagglutinin of A/N-WS/33 influenza virus recombinants influencing sensitivity to trypsin and antigenic reactivity, Virology 107:320–330.PubMedGoogle Scholar
  22. Fazekas de St. Groth, S., 1963, Steric inhibition: Neutralization of a virus-borne enzyme, Ann. N.Y. Acad. Sci. 103:674–687.Google Scholar
  23. Fields, S., Winter, G., and Brownlee, G. G., 1981, Structure of the neuraminidase gene from human influenza virus A/PR/8/34, Nature 290:213–217.PubMedGoogle Scholar
  24. Groome, N. P., Belyavin, G., Landsdell, A., et al., 1977, Structure and composition of the N2 neuraminidase of influenza virus. Effect of carbohydrate content on the validity of molecular weight estimations, Biochim. Biophys. Acta 495:58–70.PubMedGoogle Scholar
  25. Heggeness, M. H., Smith, P. R., Ulmanen, I., et al., 1982, Studies on the helical nucleocapsid of influenza virus, Virology 118:466–470.PubMedGoogle Scholar
  26. Herrler, G., Nagele, A., Meier-Ewert, H., et al., 1981, Isolation and structural analysis of influenza C virion glycoproteins, Virology 113:439–451.PubMedGoogle Scholar
  27. Herrler, G., Rott, R.,Klenk, H-D., et al., 1985, The receptor-destroying, enzyme of influenza C virus is neuraminate-O-acetylesterase. EM BO Journal 4:1503–1506.Google Scholar
  28. Huang, R. T. C., 1976, Sphingolipids of influenza viruses, Biochim. Biophys. Acta 424:90–97.PubMedGoogle Scholar
  29. Huang, R. T. C., Wahn, K., Klenk, H.-D., et al., 1980, Fusion between cell membranes and liposomes containing the glycoprotein of influenza virus, Virology 104:294–302.PubMedGoogle Scholar
  30. Jackson, D. C., Brown, L. E., and White, D. O., 1981, Antigenic determinants of influenza virus hemagglutinin. VI. Antigenic characterization of the oligosaccharide sidechains from HA of influenza virus hemagglutinins, J.. Gen. Virol 52:163–168.PubMedGoogle Scholar
  31. Jennings, P. A., Finch, J. T., Winter, G., et al., 1983, Does the higher order structure of the influenza virus ribonucleoprotein guide sequence rearrangements in influenza viral RNA? Cell 34:619–627.PubMedGoogle Scholar
  32. Karadaghi, S. E., Zakomirdin, J. A., Shimane, C., et al., 1984, Interaction of influenza virus proteins with planar bilayer lipid membranes. I. Characterization of their adsorption and incorporation into lipid bilayers, Biochim. Biophys. Acta 778:269–275.PubMedGoogle Scholar
  33. Kates, M., Allison, A. C., Tyrrell, D. A. J., et al., 1961, Lipids of influenza virus and their relation to those of the host cell, Biochim. Biophys. Acta 52:455–466.Google Scholar
  34. Kawakami, K., Ishihama, A., and Hamaguchi, M., 1981, RNA polymerase of influenza virus. I. Comparison of the virion-associated RNA polymerase activity of various strains of influenza virus, J.. Biochem. 89:1751–1757.PubMedGoogle Scholar
  35. Keil, W., Klenk, H.-D., and Schwarz, R. T., 1979, Carbohydrates of influenza virus. III. Nature of oligosaccharide-protein linkage in viral glycoproteins,J.. Virol. 31:253–256.PubMedGoogle Scholar
  36. Keil, W., Geyer, R., Niemann, H., et al., 1984a, The carbohydrates of the hemagglutinin of influenza virus, in: Segmented Negative Strand Viruses (R. Compans and D. Bishop, eds.), Academic Press, New York, pp. 289–298.Google Scholar
  37. Keil, W., Niemann, H., Schwarz, R. T., et al., 1984b, Carbohydrates of influenza virus. V. Oligosaccharides attached to individual glycosylation sites of the hemagglutinin of fowl plague virus, Virology 133:77–91.PubMedGoogle Scholar
  38. Kendal, A. P., and Eckert, E., 1972, The preparation and properties of 14C-carboxamidomethylated subunits from A/1957 influenza neuraminidase, Biochim. Biophys. Acta 258:484–495.PubMedGoogle Scholar
  39. Kendal, A. P., and Madeley, C. R., 1970, Flocculation of influenza virus by specific antineuramini dase antibody, Arch. Ges. Virusforsch. 31:219–229.PubMedGoogle Scholar
  40. Kharitonenkov, I. G., Siniakov, M. S., Grigoriev, V. B., et al., 1978, The length of the influenza virus spikes measured by photon correlation spectroscopy, FEBS Lett. 96:120–124.PubMedGoogle Scholar
  41. Kilbourne, E. D., 1963, Influenza virus genetics, Prog. Med. Virol. 5:79–126.Google Scholar
  42. Kilbourne, E. D., 1969, Future influenza vaccines and the use of genetic recombinants, Bull. WHO 41:643–645.PubMedGoogle Scholar
  43. Kilbourne, E. D., and Murphy, J. S., 1960, Genetic studies of influenza viruses. I. Viral morphology and growth capacity as exchangeable genetic traits. Rapid in ovo adaptation of early passage Asian strain isolates by combination with PR8, J.. Exp. Med. 111:387–406.PubMedGoogle Scholar
  44. Kilbourne, E. D., Palese, P., and Schulman, J. L., 1975, Inhibition of viral neuraminidase as a new approach to the prevention of influenza, in: Perspectives in Virology ,Vol. IX (M. Pollard, ed.), Academic Press, New York, pp. 99–113.Google Scholar
  45. Klenk, H.-D., 1980, Processing of the haemagglutinin: Glycosylation and proteolytic cleavage, in: Structure and Variation in Influenza Virus (G. Laver and G. Air, eds.), Elsevier/North Holland, Amsterdam, pp. 213–222.Google Scholar
  46. Klenk, H.-D., Rott, R., Orlich, M., et al., 1975, Activation of influenza A viruses by trypsin treatment, Virology 68:426–439.PubMedGoogle Scholar
  47. Klenk, H.-D., Keil, W., Niemann, H., et al., 1983, The characterization of influenza A viruses by carbohydrate analysis, Curr. Top. Microbiol. Immunol. 104:247–257.PubMedGoogle Scholar
  48. Knossow, M., Daniels, R. S., Douglas, A. R., et al., 1984, Three-dimensional structure of an antigenic mutant of the influenza virus hemagglutinin, Nature 311:678–680.PubMedGoogle Scholar
  49. Krystal, M., Young, J. F., Palese, P., et al., 1983, Sequential mutations in hemagglutinins of influenza B virus isolates: Definition of antigenic domains, Proc. Natl. Acad. Sci. U.S.A. 80:4527–4531.PubMedGoogle Scholar
  50. Lamb, R. A., 1983, The influenza virus RNA segments and their encoded proteins, in: Genetics of Influenza Viruses (P. Palese and D. W. Kingsbury, eds.), New York, pp. 21–69.Google Scholar
  51. Laver, W. G., and Kilbourne, E. D., 1966, Identification in a recombinant influenza virus of structural proteins derived from both parents, Virology 30:493–501.PubMedGoogle Scholar
  52. Laver, W. G., and Valentine, R. C., 1969, Morphology of the isolated hemagglutinin and neuraminidase subunits of influenza virus, Virology 38:105–119.PubMedGoogle Scholar
  53. Laver, W. G., and Webster, R. G., 1966, The structure of influenza virus. IV. Chemical studies of the host antigen, Virology 30:104–115.PubMedGoogle Scholar
  54. Lazarowitz, S. G., and Choppin, P. W., 1975, Enhancement of infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide, Virology 68:440–454.PubMedGoogle Scholar
  55. Lazdins, I., Haslam, E. A., and White, D. O., 1972, The polypeptides of influenza virus. VI. Composition of the neuraminidase, Virology 49:758–765.PubMedGoogle Scholar
  56. Londo, D. R., Davis, A. R., and Nayak, D. P., 1983, Complete nucleotide sequence of the nucleoprotein gene of influenza B virus, J.. Virol 47:642–648.PubMedGoogle Scholar
  57. Martin, M. L., Palmer, E. L., and Kendal, A. P., 1977, Lack of characteristic hexagonal surface structure on a newly isolated influenza C virus, J.. Clin. Microbiol. 6:84–86.PubMedGoogle Scholar
  58. Murti, K. G., Bean, W. J., Jr., and Webster, R. G., 1980, Helical ribonucleoproteins of influenza virus: An electron microscopic analysis, Virology 104:224–229.PubMedGoogle Scholar
  59. Murti, K. G., and Webster, R. G., 1986, Distribution of hemagglutinin and neuraminidase on influenza virions as revealed by immunoelectron microscopy, Virology 149:36–43.PubMedGoogle Scholar
  60. Nakada, S., Creager, R. S., Krystal, M., et al., 1984a, Influenza C virus hemagglutinin: Comparison with influenza A and B virus hemagglutinins,J.. Virol. 50:118–124.PubMedGoogle Scholar
  61. Nakada, S., Creager, R. S., Krystal, M., et al., 1984b, Complete nucleotide sequence of the influenza C/California/78 virus nucleoprotein gene, Virus Res. 1:433–441.PubMedGoogle Scholar
  62. Nakada, S., Graves, P. N., Desselberger, U., et al., 1985, Influenza C virus RNA 7 codes for a nonstructural protein, J.. Virol. 56:221–226.PubMedGoogle Scholar
  63. Nakamura, K., and Compans, R. W., 1979, Host cell and virus strain-dependent differences in oligosaccharides of hemagglutinin glycoproteins of influenza A viruses, Virology 95:8–23.PubMedGoogle Scholar
  64. Nayak, D. P., 1980, Defective interfering influenza viruses, Annu. Rev. Microbiol. 34:619–644.PubMedGoogle Scholar
  65. Nermut, M. V.,, 1972, Further investigation on the fine structure of influenza virus, J.. Gen. Virol. 17:317–331.PubMedGoogle Scholar
  66. Nermut, M. V., and Frank, H., 1971, Fine structure of influenza A2 (Singapore) as revealed by negative staining, freeze-drying and freeze-etching, J.. Gen. Virol. 10:37–51.PubMedGoogle Scholar
  67. Nestorowicz, A., Laver, G., and Jackson, D. C., 1985, Antigenic determinants of influenza virus hemagglutinin. X. A comparison of the physical and antigenic properties of monomeric and trimeric forms, J.. Gen. Virol. 66:1687–1695.PubMedGoogle Scholar
  68. Pfeifer, J. B., and Compans, R. W., 1984, Structure of the influenza C glycoprotein gene as determined from cloned DNA, Virus Res. 1:281–296.PubMedGoogle Scholar
  69. Pons, M. W., Schulze, I. T., Hirst, G. K., et al., 1969, Isolation and characterization of the ribonucleoprotein of influenza virus, Virology 39:250–259.PubMedGoogle Scholar
  70. Racaniello, V. R., and Palese, P., 1979, Influenza B virus genome: Assignment of viral polypeptides to RNA segments,J. Virol. 29:361–373.PubMedGoogle Scholar
  71. Robertson, J. S., Robertson, M. E. St. C., and Roditi, I. J., 1984, Nucleotide sequence of RNA segment 3 of the avian influenza A/FPV/Rostock/34 and its comparison with the corresponding segment of human strains A/PR/8/34 and A/NT/60/68, Virus Res. 1:73–79.Google Scholar
  72. Roditi, I. J., and Robertson, J. S., 1984, Nucleotide sequence of the avian influenza virus A/fowl plague/Rostock/34 segment 1 encoding the PB2 polypeptide, Virus Res. 1:65–71.Google Scholar
  73. Ruigrok, R. W. H., Andree, P. J., Hooft Van Huysduynen, R. A. M., et al., 1984, Characterization of three highly purified influenza virus strains by electronmicroscopy, J. Gen. Virol. 65:799–802.PubMedGoogle Scholar
  74. Ruigrok, R. W. H., Krijgsman, P. C. J., deRonde-Verloop, F. M., et al., 1985, Natural heterogeneity of shape, infectivity and protein composition in an influenza A (H3N2) virus preparation, Virus. Res. 3:69–76.PubMedGoogle Scholar
  75. Schmidt, M. F. G., 1982, Acylation of viral spike glycoproteins: A feature of enveloped RNA viruses, Virology 116:327–338.PubMedGoogle Scholar
  76. Schmidt, M. F. G., 1984, The transfer of myristic and other fatty acids on lipid and viral protein acceptors in cultured cells infected with Semliki Forest and influenza virus, EMBOJ. 3:2295–2300.Google Scholar
  77. Shaw, M. W., Lamb, R. A., Erickson, B. W., et al., 1982, Complete nucleotide sequence of the neuraminidase gene of influenza B virus, Proc. Natl. Acad. Sci. U.S.A. 79:6817–6821.PubMedGoogle Scholar
  78. Shaw, M. W., Choppin, P. W., and Lamb, R. A., 1983, A previously unrecognized influenza B virus glycoprotein from a bicistronic mRNA that also encodes the viral neuraminidase, Proc. Natl. Acad. Sci. U.S.A. 80:4879–4883.PubMedGoogle Scholar
  79. Singer, S. J., and Nicolson, G. L., 1972, The fluid mosaic model of the structure of cell membranes, Science 175:720–731.PubMedGoogle Scholar
  80. Sivasubramanian, N., and Nayak, D. P., 1982, Sequence analysis of the polymerase 1 gene and the secondary structure prediction of polymerase 1 protein of human influenza virus A/WSN/33, J. Virol. 44:321–329.PubMedGoogle Scholar
  81. Skehel, J. J., Hay, A. J., and Waterfield, M. D., 1980, Influenza-virus, in: Cell Membranes and Viral Envelopes ,Vol. 2 (H. A. Blough and J. M. Tiffany, eds.), Academic Press, London, pp. 647–681.Google Scholar
  82. Skehel, J. J., Stevens, D. J., Daniels, R. S., et al., 1984, A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody, Proc. Natl. Acad. Sci. U.S.A. 81:1779–1783.PubMedGoogle Scholar
  83. Sleigh, M. J., Both, G. W., and Brownlee, G. G., 1979, A new method for the size estimation of the RNA genome segments of influenza virus, Nucleic Acids Res. 6:1309–1321.PubMedGoogle Scholar
  84. Taylor, R. B., Duffus, W. P. H., Raff, M. C., et al., 1971, Redistribution and pinocytosis of lymphocyte surface immunoglobulin molecules induced by anti-immunoglobulin antibody, Nature (New Biol. 1 233:225–229.Google Scholar
  85. Tobita, K., and Kilbourne, E. D., 1974, Genetic recombination for antigenic markers of antigenically different strains of influenza B virus, J. Virol 13:347–352.PubMedGoogle Scholar
  86. Varghese, J. N., Laver, W. G., and Colman, P. M., 1983, Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution, Nature 303:35–40.PubMedGoogle Scholar
  87. Verhoryen, M., Fang, R., Min Jou, W., et al., 1980, Antigenic drift between the hemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75, Nature 286:771–775.Google Scholar
  88. Ward, C. W., 1981, Structure of the influenza virus hemagglutinin, Curr. Top. Microbiol. Immunol. 94/95:1–74.Google Scholar
  89. Ward, C. W., and Dopheide, T. A. A., 1979, Primary structure of the Hong Kong (H3) hemagglutinin, Br. Med. Bull. 35:51–56.PubMedGoogle Scholar
  90. Ward, C. W., and Dopheide, T. A. A., 1980, The Hong Kong (H3) hemagglutinin. Complete amino acid sequence and oligosaccharide distribution for the heavy chain of A/Memphis/102/72, in: Structure and Variation of Influenza Virus (W. G. Laver and G. Air, eds.), Elsevier, Amsterdam, pp. 27–38.Google Scholar
  91. Ward, C. W., Murray, J. M., Roxburgh, C. M., et al., 1983, Chemical and antigenic characterization of the carbohydrate side chains of an Asian (N2) influenza virus neuraminidase, Virology 126:370–375.PubMedGoogle Scholar
  92. Waterfield, M. D., Espelie, K., Elder, K., et al., 1979, Structure of the hemagglutinin of influenza virus, Br. Med. Bull. 35:56–67.Google Scholar
  93. Wiley, D. C., Wilson, I. A., and Skehel, J. J., 1981, Structural identification of the antibody-binding sites of Hong Kong influenza hemagglutinin and their involvement in antigenic variation, Nature 289:373–378.PubMedGoogle Scholar
  94. Wiley, D. C., Wilson, I. A., and Skehel, J. J., 1984, The hemagglutinin membrane glycoprotein of influenza virus, Biol. Macromol. Assemblies 1:299–336.Google Scholar
  95. Wilson, I. A., Skehel, J. J., and Wiley, D. C., 1981, Structure of the hemagglutinin membrane glycoprotein of influenza virus at 3 A resolution, Nature 289:366–373.PubMedGoogle Scholar
  96. Wilson, I. A., Ladner, R. C., Skehel, J. J., et al., 1983, The structure and role of the carbohydrate moieties of influenza virus hemagglutinin, Biochem. Soc. Trans. 11:145–147.Google Scholar
  97. Wilson, J. C., Tudor, L. R., and Darlington, R. W., 1977, Morphology of influenza virions from the infected host, Am. Soc. Microbiol. Abstr.Google Scholar
  98. Winter, G., and Fields, S., 1982, Nucleotide sequence of human influenza A/PR/8/34 segment 2, Nucleic Acids Res. 10:2135–2143.PubMedGoogle Scholar
  99. Wrigley, N. G., 1979, Electron microscopy of influenza virus, Br. Med. Bull. 35:35–38.PubMedGoogle Scholar
  100. Wrigley, N. G., Skehel, J. J., Charlwood, P. A., et al., 1973, The size and shape of influenza virus neuraminidase, Virology 51:525–529.PubMedGoogle Scholar
  101. Wrigley, N. G., Brown, E. B., Daniels, R. S., et al., 1983, Electron microscopy of influenza haemagglutinin-monoclonal antibody complexes, Virology 131:308–314.PubMedGoogle Scholar

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© Edwin D. Kilbourne, M.D. 1987

Authors and Affiliations

  • Edwin D. Kilbourne
    • 1
  1. 1.Mount Sinai School of MedicineCity University of New YorkNew YorkUSA

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