Proteolysis, a Determinant for Virus Pathogenicity

  • H. D. Klenk
  • F. X. Bosch
  • W. Garten
  • T. Kohama
  • Y. Nagai
  • R. Rott
Part of the Colloquium der Gesellschaft für Biologische Chemie 26.–28. April 1979 in Mosbach/Baden book series (MOSBACH, volume 30)

Abstract

Pathogenicity, i.e., the ability of a virus to induce disease in the infected organism, is the result of a complex interplay of a multitude of factors that are determined by the biological, biochemical, and genetic characteristics of the virus on the one hand, and the reactivity of the host on the other. Thus, a molecular basis for viral pathogenicity is not easy to define. It is reasonable, however, to assume that clinical disease becomes manifest, if cells of vital function are altered or killed by the infecting virus. Since the tropism of a virus for a host cell represents primarily an interaction between the surface components of the virus and receptors of the host cell, it is appealing to postulate that surface structures of a virus might determine pathogenicity. This concept is supported by recent results obtained with myxoviruses. It will be shown that the surface glycoproteins of these viruses acquire biological activity through proteolytic cleavage and that this activation is of high importance for pathogenicity.

Keywords

Migration Carbohydrate Bromide Influenza Electrophoresis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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
  2. Compans RW, Klenk H-D (1979) Viral membranes. In: Fraenkel-Conrat H, Wagner RR (eds) Comprehensive virology. Plenum Press, New York, in pressGoogle Scholar
  3. 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
  4. Homma M, Ohuchi M (1973) Trypsin action on the growth of Sendai virus in tissue culture cells. III. Structural difference of Sendai virus grown in eggs and in tissue culture. J Virol 12: 1457–1465Google Scholar
  5. Klenk H-D, Rott R, Orlich M, Blodorn J (1975) Activation of influenza viruses by trypsin treatment. Virology 68: 426–439PubMedCrossRefGoogle Scholar
  6. 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
  7. Kurrle R, Wagner H, Rollinghoff M, Rott R (1979) Influenza virus-specific T cell mediated cytotoxicity: Integration of the virus antigen into the target cell membrane is essential for target cell formation. Eur J Immunol 9: 107–111Google Scholar
  8. Lazarowitz SG, Choppin PW (1975) Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology 48: 440–454CrossRefGoogle Scholar
  9. Lazarowitz SG, Compans RW, Choppin PW (1973) Proteolytic cleavage of the hemagglutinin polypeptide of influenza virus. Function of the uncleaved polypeptide HA. Virology 52: 199–212Google Scholar
  10. Moore NP, Burke DC (1974) Characterization of the structural proteins of different strains of Newcastle disease virus. J Gen Virol 25: 275–289PubMedCrossRefGoogle Scholar
  11. Nagai Y, Klenk H-D (1977) Activation of precursors to both glycoproteins of NDV by proteolytic cleavage. Virology 77: 125–134PubMedCrossRefGoogle Scholar
  12. Nagai Y, Klenk H-D, Rott R (1976a) Proteolytic cleavage of the viral glycoproteins and its significance for the virulence of Newcastle disease virus. Virology 72: 494–508PubMedCrossRefGoogle Scholar
  13. Nagai Y, Ogura H, Klenk H-D (1976b) Studies on the assembly of the envelope of Newcastle disease virus. Virology 69: 523–538PubMedCrossRefGoogle Scholar
  14. Nagai Y, Shimokata K, Yoshida T, Hamaguchi M, Iinuma M, Maeno K, Matsumoto T, Klenk H-D, Rott R (1979) The spread of a pathogenic and an apathogenic strain of Newcastle disease virus in the chick embryo as depending on the protease sensitivity of the viral glycoproteins. J Gen Virol submittedGoogle Scholar
  15. Nicolau C, Klenk H-D, Reimann A, Hildenbrand K, Bauer H (1978) Molecular events during the interaction of envelopes of myxo- and RNA-tumor viruses with cell membranes. Biochim Biophys Acta 511: 83–92PubMedCrossRefGoogle Scholar
  16. Rott R (1979) Molecular basis of infectivity and pathogenicity of myxovirus. Arch Virol 59: 285–298PubMedCrossRefGoogle Scholar
  17. Rott R, Klenk H-D (1977) Structure and assembly of viral envelopes. In: Poste G, Nicolson GL (eds) Virus infection and the cell surface. Cell surface reviews, vol II. Elsevier, Amsterdam, p 47–81Google Scholar
  18. Scheid A, Choppin PW (1973) Isolation and purification of the envelope proteins of Newcastle disease virus. J Virol 11: 263–271PubMedGoogle Scholar
  19. Scheid A, Choppin PW (1974) Identification of biological activities of paramyxovirus glycoproteins. Activation of cell fusion, hemolysis, and infectivity by proteolytic cleavage of an inactive precursor protein of Sendai virus. Virology 57: 475–490Google Scholar
  20. Scheid A, Choppin PW (1977) Two disulfide linked polypeptide chains constitute the active F protein of paramyxoviruses. Virology 80: 54–66PubMedCrossRefGoogle Scholar
  21. Scheid A, Caliguiri LA, Compans RW, Choppin PW (1972) Isolation of paramyxovirus glycoproteins. Association of both hemagglutinating and neuraminidase activities with the larger SV5 glycoprotein. Virology 50: 640–652PubMedCrossRefGoogle Scholar
  22. Seto JT, Becht H, Rott R (1973) Isolation and purification of surface antigens from disrupted paramyxoviruses. Med Microbiol Immunol 159: 1–12PubMedCrossRefGoogle Scholar
  23. Shimizu K, Shimizu YK, Kohama T, Ishida N (1974) Isolation and characterization of two distinct types of HVJ ( Sendai virus) spikes. Virology 62: 90–101Google Scholar
  24. Tozawa H, Watanabe M, Ishida N (1973) Structural components of Sendai virus. Serological and physicochemical characterization of hemagglutinin subunit associated with neuraminidase activity. Virology 55: 242–253Google Scholar
  25. Waterson AP, Pennington TH, Allan WH (1967) Virulence in Newcastle disease virus. A preliminary study. Br Med Bull 23: 138–143Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1979

Authors and Affiliations

  • H. D. Klenk
  • F. X. Bosch
  • W. Garten
  • T. Kohama
  • Y. Nagai
  • R. Rott
    • 1
  1. 1.Institut für VirologieJustus-Liebig-Universität Gießen63 Gießen/LahnGermany

Personalised recommendations