Viral Glycoproteins as Determinants of Pathogenicity

  • H.-D. Klenk
  • M. Tashiro
  • W. Garten
  • R. Rott
Conference paper
Part of the Colloquium der Gesellschaft für Biologische Chemie 9.–11. April 1987 in Mosbach/Baden book series (MOSBACH, volume 38)

Abstract

Many viruses possess a lipid-containing envelope which is a simple biological membrane surrounding the viral genome and accessory proteins. Among the general features of membrane structure shared by all of these viruses are glycoproteins that span the lipid bilayer and usually appear as protrusions or spikes at the surface of the virus particles. Viral glycoproteins have found wide interest as models for structure and biosynthesis of membrane proteins. Moreover, they are the major targets for the humoral and cellular immune response against the virus. This chapter will deal with another important aspect of these glycoproteins, namely their key role in virus entry into the host cell and their significance as determinants of virus pathogenicity. Our knowledge on the role of viral glycoproteins as initiatiors of infection and determinants of pathogenicity has been derived mainly from studies on ortho-and paramyxoviruses. We will therefore concentrate here on these viruses, but we will also present evidence that similar concepts may also be relevant for other viruses.

Keywords

Influenza Polypeptide Trypsin Oligosaccharide Plasminogen 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Air GM, Laver WG (1986) The molecular basis of antigenic variation in influenza virus. Adv Virus Res 31:53–102PubMedCrossRefGoogle Scholar
  2. Auperin DD, Sasso DR, McCormick JB (1986) Nucleotide sequence of the glycoprotein gene and intergenic region of the Lassa virus S genome RNA. Virology 154:155–167PubMedCrossRefGoogle Scholar
  3. Binns MM, Boursnell MEG, Cavanagh D, Pappin DJC, Brown TDK (1985) Cloning and sequencing of the gene encoding the spike protein of the coronavirus JBV. J Gen Virol 66:719–726PubMedCrossRefGoogle Scholar
  4. Blumberg BM, Giorgi C, Rose K, Kolakovsky D (1985) Sequence determination of the Sendai virus fusion protein gene. J Gen Virol 66:317–331PubMedCrossRefGoogle Scholar
  5. Bosch FX, Orlich M, Klenk H-D, Rott R (1979) The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. Virology 95:197–207PubMedCrossRefGoogle Scholar
  6. Bosch FX, Garten W, Klenk H-D, Rott R (1981) Proteolytic cleavage of influenza virus hemagglutinins. Primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of avian influenza viruses. Virology 113:725–735PubMedCrossRefGoogle Scholar
  7. Chambers P, Miller NS, Emmerson PT (1986b) Nucleotide sequence of the chain gene encoding the fusion glycoprotein of Newcastle disease virus. J Gen Virol 67: 2685–2694PubMedCrossRefGoogle Scholar
  8. Collins PL, Huang AT, Wertz GW (1984) Nucleotide sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus. Proc Natl Acad Sci USA 81:7683–7687PubMedCrossRefGoogle Scholar
  9. Docherty K, Steiner DF (1982) Post-translational proteolysis in polypeptide hormone biosynthesis. Annu Rev Physiol 44:625–638PubMedCrossRefGoogle Scholar
  10. Fang R, Min-Jou W, Huylebroeck D, Devos R, Fiers W (1981) Complete structure of A/ duck/Ukraine/63 influenza hemagglutinin gene: animal virus as progenitor of human H3 Hong Kong 1968 influenza hemagglutinin. Cell 25:315–323PubMedCrossRefGoogle Scholar
  11. Feldmann H (1988) The nucleotide sequence of the hemagglutinin gene of the influenza virus A/chick/Germany/49 (H10N7). Thesis, Philipps Univ, MarburgGoogle Scholar
  12. Garoff H, Frischauf A-M, Simons K, Lehrach H, Delius H (1980) Nucleotide sequence of cDNA coding for Semliki Forest virus membrane glycoproteins. Nature (London) 288:236–241CrossRefGoogle Scholar
  13. Garten W, Berk W, Nagai Y, Rott R, Klenk H-D (1980) Mutational changes of the protease susceptibility of glycoprotein F of Newcastle Disease Virus: Effects on pathogenicity. J Gen Virol 50:135–147PubMedCrossRefGoogle Scholar
  14. Garten W, Bosch FX, Linder D, Rott R, Klenk H-D (1981) Proteolytic activation of the influenza hemagglutinin: The structure of the cleavage site and the enzymes involved in cleavage. Virology 115:361–374PubMedCrossRefGoogle Scholar
  15. Garten W, Linder D, Rott R, Klenk H-D (1982) The cleavage site ’of the hemagglutinin of fowl plague virus. Virology 122:186–190PubMedCrossRefGoogle Scholar
  16. Garten W, Klenk H-D (1983) Characterization of the carboxypeptidase involved in the proteolytic cleavage of the influenza haemagglutinin. J Gen Virol 64:2127–2137PubMedCrossRefGoogle Scholar
  17. Garten W, Kuroda K, Schuy W, Naruse H, Scholtissek C, Klenk H-D (1985) Haemagglutinin transport mutants. Vaccine Suppl 3:227–229CrossRefGoogle Scholar
  18. Gething MJ, White JM, Waterfield MD (1978) Purification of the fusion protein of Sendai virus: Analysis of the NH2-terminal sequence generated during precursor activation. Proc Natl Acad Sci USA 75:2737–2740PubMedCrossRefGoogle Scholar
  19. Gething MJ, Bye J, Skehel JJ, Waterfield MD (1980) Cloning and DNA sequence of double-stranded copies of hemagglutinin genes from H2 and H3 strains elucidates antigenic shift and drift in human influenza virus. Nature (London) 287:301–306CrossRefGoogle Scholar
  20. Higa HH, Rogers GN, Paulson JC (1985) Influenza virus hemagglutinins differentiate between receptor determinants bearing N-acetyl-, N-glycollyl-and N,O-diacetyl neuraminic acids. Virology 144:279–282PubMedCrossRefGoogle Scholar
  21. Homma M, Ohuchi M (1973) Trypsin action on the growth of Sendai virus in tissue culture cells. III. Structural difference of Sendai viruses grown in eggs and in tissue culture cells. J Virol 12:1457–1465PubMedGoogle Scholar
  22. Hsu M-C, Scheid A, Choppin PW (1987) Protease activation mutants of Sendai virus: sequence analysis of the mRNA of the fusion protein (F) gene and direct identification of the cleavage-activation site. Virology 156:84–90PubMedCrossRefGoogle Scholar
  23. Huang RTC, Rott R, Klenk H-D (1981) Influenza viruses cause hemolysis and fusion of cells. Virology 110:243–247PubMedCrossRefGoogle Scholar
  24. Kalica AR, Flores I, Greenberg HB (1983) Identification of the rotaviral gene that codes for hemagglutination and protease-enhanced plaque formation. Virology 125:194–205PubMedCrossRefGoogle Scholar
  25. Kawaoka Y, Webster RG (1985) Evolution of the A/chicken/Pennsylvania/83 (H5N2) influenza virus. Virology 146:130–137PubMedCrossRefGoogle Scholar
  26. Kawaoka Y, Naeve, CW, Webster RG (1984) Is virulence of H5N2 influenza viruses in chickens associated with loss of cabohydrate from the hemagglutinin? Virology 139:303–316PubMedCrossRefGoogle Scholar
  27. Keil W, Geyer R, Dabrowski J, Dabrowski U, Niemann H, Stirm S, Klenk H-D (1985) Carbohydrates of influenza virus IV. Structural elucidation of the individual gly-cans of the FPV hemagglutinin by two-dimensional 1H NMR and methylation analysis. EMBO J 4:2711–2720PubMedGoogle Scholar
  28. Klenk H-D, Rott R (1980) Cotranslational and posttranslational processing of viral glycoproteins. Curr Top Microbiol Immunol 90:19–48PubMedCrossRefGoogle Scholar
  29. Klenk H-D, Rott R, Orlich M, Blödorn J (1975) Activation of influenza A viruses by trypsin treatment. Virology 68:426–439PubMedCrossRefGoogle Scholar
  30. Klenk H-D, Rott R, Orlich M (1977) Further studies on the activation of influenza virus by proteolytic cleavage of the hemagglutinin. J Gen Virol 36:151–161PubMedCrossRefGoogle Scholar
  31. Klenk H-D, Garten W, Bosch FX, Rott R (1984) The role of the haemagglutinin as a determinant for the pathogenicity of avian influenza viruses. In: Stuart Harris C, Potter CW (eds) The molecular virology and epidemiology of influenza. Academic Press, London New York, pp 195–209Google Scholar
  32. Lamb RA (1983) The influenza virus RNA segments and their encoded proteins. In: Pa-lese P, Kingsbury DW (eds) Genetics of influenza virus. Springer Berlin Heidelberg New York, pp 21–69Google Scholar
  33. Lazarowitz SG, Choppin PW (1975) Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology 68: 440–454PubMedCrossRefGoogle Scholar
  34. Lazarowitz SG, Goldberg AR, Choppin PW (1973) Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus. Host cell activation of serum plasminogen. Virology 56:172–180PubMedCrossRefGoogle Scholar
  35. Lpez S, Arias CF, Méndez E, Espejo RT (1986) Conservation in rotaviruses of the protein region containing the two sites associated with trypsin enhancement of infectivity. Virology 154:224–227CrossRefGoogle Scholar
  36. McGinnes CW, Morrison TK (1986) Nucleotide sequence of the gene encoding the new-catle disease virus fusion protein and comparisons of paramyxovirus fusion protein synthesis. Virus Res 5:342–356CrossRefGoogle Scholar
  37. Naeve CW, Webster RG (1983) Sequence of the haemagglutinin gene from influenza virus A/Seal/Mass/1/80. Virology 129:298–308PubMedCrossRefGoogle Scholar
  38. Nagai Y, Klenk H-D (1977) Activation of precursors to both glycoproteins of New-catle disease virus by proteolytic cleavage. Virology 77:125–134PubMedCrossRefGoogle Scholar
  39. Nagai Y, Klenk H-D, Rott R (1976) Proteolytic cleavage of the viral glycoproteins and its significance for the virulence of Newcastle disease virus. Virology 72: 494–508PubMedCrossRefGoogle Scholar
  40. Offit PA, Blavat G, Greenberg HB, Clark HF (1986) Molecular basis of rota-virus virulence: role of gene segment 4. J Virol 57:46–49PubMedGoogle Scholar
  41. Paterson RG, Harris TJR, Lamb RA (1984) Fusion protein of the paramyxovirus SV5: Nucleotide sequence of mRNA predicts a highly hydrophobic glycoprotein. Proc Natl Acad Sci USA 81:6706–6710PubMedCrossRefGoogle Scholar
  42. Porter AG, Barber C, Carey NH, Hallewell RA, Threfall G, Emtage JS (1979) Complete nucleotide sequence of an influenza virus hemagglutinin gene from cloned DNA. Nature (London) 282:471–477CrossRefGoogle Scholar
  43. Pritzer E (1985) The nucleotide sequence of the hemagglutinin gene of the fowl plague virus strain A/FPV/Dutch/27. Thesis, Justus-Liebig-Univ, GießenGoogle Scholar
  44. Ratner C, Haseltine W, Patarce R, Livak KJ, Starcich B, Josephs SF, Dovan ER, Ra-faski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR, Pearson ML, Lauten-berger JA, Papas TS, Ghrayes I, Chang NT, Gallo RC, Wong-Staal F (1985) Complete nucleotide sequence of the AIDS virus, HTLV III. Nature (London) 313:277–284CrossRefGoogle Scholar
  45. Rice JM, Strauss JH (1981) Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins. Proc Natl Acad Sci USA 78:2062–2066PubMedCrossRefGoogle Scholar
  46. Richardson C, Hull D, Greer P, Hasel K, Berkovich A, Englund G, Bellini W, Rima B, Lazzarini R (1986) The nucleotide sequence of the mRNA encoding the fusion protein of measles virus (Edmonston strain): A comparison of fusion proteins from several different paramyxoviruses. Virology 155:508–523PubMedCrossRefGoogle Scholar
  47. Richardson CR, Scheid A, Choppin PW (1980) Specific inhibition of paramyxovirus and myxovirus replication by oligopeptides with amino acid sequences similar to those at the N-termini of Fl or HA2 viral polypeptides. Virology 105:205–222PubMedCrossRefGoogle Scholar
  48. Robertson L, Caley IP, Moore I (1958) Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet 2:233–236PubMedCrossRefGoogle Scholar
  49. Rogers GN, Paulson JC (1983) Receptor determinants of human and animal influenza virus isolates: Differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127:361–373PubMedCrossRefGoogle Scholar
  50. Rogers GN, Herrier G, Paulson JC, Klenk H-D (1986) Influenza C virus uses 9-0-acetyl-N-acetylneuraminic acid as a high affinity receptor determinant for attachment to cells. J Biol Chem 261:5947–5951PubMedGoogle Scholar
  51. Rott R, Klenk H-D (1986) Pathogenicity of influenza virus in model systems. In: Kendal AP, Patriarca PA (eds) Options for the control of influenza. Liss, New York, pp 53–62Google Scholar
  52. Rott R, Reinacher M, Orlich M, Klenk H-D (1980) Cleavability of hemagglutinin determines spread of avian influenza viruses in the chorioallantoic membrane of chicken embryo. Arch Virol 65:123–133PubMedCrossRefGoogle Scholar
  53. Rott R, Orlich M, Klenk H-D, Wang ML, Skehel JJ, Wiley JC (1984) Studies on the adaptation of influenza viruses to MDCK cells. EMBO J 3:3329–3332PubMedGoogle Scholar
  54. Scheid A, Choppin PW (1974) Identification of biological activities of paramyxovirus glycoproteins activation of cell fusion, hemolysis, and infectivity by proteoly-tic cleavage of an inactive precursor protein of Sendai virus. Virology 57:475– 490PubMedCrossRefGoogle Scholar
  55. Scheid A, Choppin PW (1976) Protease activation mutants of Sendai: Activation of biological properties by specific proteases. Virology 69:265–277PubMedCrossRefGoogle Scholar
  56. Scheid A, Caliguiri LA, Compans RW, Choppin PW (1972) Isolation of paramyxovirus glycoproteinso Association of both hemagglutinin and neuraminidase activities with the larger SV5 glycoprotein. Virology 50:640–652PubMedCrossRefGoogle Scholar
  57. Scheid A, Graves MC, Silver SM, Choppin PW (1978) Studies on the structure and function of paramyxovirus proteins. In: Mahy BWJ, Barry RD (eds) Negative strand viruses and the host cell. Academic Press, London New York, pp 181–193Google Scholar
  58. Schuy W, Garten W, Linder D, Klenk H-D (1984) The carboxyterminus of the hemaggluti-nin-neuraminidase of Newcastle disease virus is exposed at the surface of the viral envelope. Virus Res 1:415–426PubMedCrossRefGoogle Scholar
  59. Schwarz D, Tizard R, Gilbert W (1983) Nucleotide sequence of Rous sarcoma virus. Cell 32:853–869CrossRefGoogle Scholar
  60. Server AC, Smith JA, Waxham MN, Wolinsky JS, Goodman HM (1985) Purification and amino terminal protein sequence analysis of the mumps virus fusion protein. Virology 144:373–383PubMedCrossRefGoogle Scholar
  61. Skehel JJ, Bayley PM, Brown EB, Martin SR, Waterfield MD, White JM, Wilson JA, Wiley DC (1982) Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci USA 79:968–972PubMedCrossRefGoogle Scholar
  62. Sleigh MJ, Both GW, Brownlee GG, Bender VJ, Moss BA (1980) The haemagglutinin gene of influenza A virus: nucleotide sequence analysis of cloned DNA copies. In: Laver G, Air GM (eds) Structure and variation in influenza viruses. Elsevier/ North Holland Biomed Press, Amsterdam New York, pp 69–79Google Scholar
  63. Spriggs MK, Olmsted RA, Venkatesan S, Coligan JE, Collins PL (1986) Fusion glyco-protein of human parainfluenza virus type 3: nucleotide sequence of the gene, direct identification of the cleavage-activation site, and comparison with other paramyxoviruseSo Virology 152:241–251Google Scholar
  64. Stuart-Harris CH, Schild GC, Oxford JS (1985) Influenza: The viruses and the disease, 2nd edn. Arnold, LondonGoogle Scholar
  65. Tashiro M, Ciborowski P, Klenk H-D, Pulverer G, Rott R (1987a) Role of Staphylococ-cus aureus in development of influenza pneumonia. Nature (London) 325:536–537CrossRefGoogle Scholar
  66. Tashiro M, Ciborowski P, Reinacher M, Pulverer G, Klenk H-D, Rott R (1987b) Syner-gistic role of Staphylococcal proteases in the induction of influenza virus pathogenicity. Virology 157:421–430PubMedCrossRefGoogle Scholar
  67. Tashiro M, Klenk H-D, Rott R (1987c) Inhibitory effect of a protease inhibitor, leu-peptin, on the development of influenza pneumonia, mediated by concomitant bacteria. J Gen Virol 68:2039–2041PubMedCrossRefGoogle Scholar
  68. Toyoda T, Sakaguchi T, Imai K, Inocencio NM, Gotoh B, Hamaguchi M, Nagai Y (1987) Structural comparison of the cleavage-activation site of the fusion glycoproteins between virulent and avirulent strains of Newcastle disease virus. Virology 158: 242–247PubMedCrossRefGoogle Scholar
  69. Wilson IA, Skehel JJ, Wiley DC (1981) The haemagglutinin membrane glycoproteins of influenza virus: structure at 3A resolution. Nature (London) 289:355–373Google Scholar
  70. Winter G, Fields S, Brownlee GG (1981) Nucleotide sequence of the haemagglutinin of a human influenza virus Hl subtype. Nature (London) 292:72–75CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • H.-D. Klenk
    • 1
  • M. Tashiro
    • 2
  • W. Garten
    • 1
  • R. Rott
    • 2
  1. 1.Institut für VirologyPhillips-UniversitätMarburgGermany
  2. 2.Institut für VirologyJustus-Liebig-UniversitätGießenGermany

Personalised recommendations