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Protective effect of protease inhibitors in influenza virus infected animals

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Summary

Injection of protease inhibitors into mice and chickens infected with lethal doses of influenza virus prevented dissemination of virus in the host organism, and had a marked protective effect. Possible mechanisms for the anti-influenza effect of protease inhibitors are discussed.

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References

  1. Alkjaersig, N., Fletcher, A. P., Sherry, S.: ε-Aminocaproic acid and inhibitor of plasminogen activation. J. Biol. Chem.234, 832–837 (1959).

    Google Scholar 

  2. Becker, W. B.: The isolation and classification of Tern virus: Influenza virus A/Tern/South Africa/1961. J. Hyg.64, 309–320 (1966).

    Google Scholar 

  3. Becker, W. B., Uys, C. J.: Experimental infection of chickens with influenza A/Tern/South Africa/1961 and Chicken/Scotland/1959 viruses. J. Comp. Path.77, 159–165 (1967).

    Google Scholar 

  4. Bosch, F. X., Orlich, M., Klenk, H.-D., Rott, R.: The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. Virology95, 197–207 (1979).

    Google Scholar 

  5. Bosch, F. X., Garten, W., Klenk, H.-D., Rott, R.: 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. Virology113, 725–735 (1981).

    Google Scholar 

  6. Brockway, W. J., Castellino, F. J.: The mechanism of the inhibition of plasmin activity by ε-Aminocaproic acid. J. Biol. Chem.246, 4641–4647 (1971).

    Google Scholar 

  7. Corey, L., Rubin, R. J., Hattwick, M. A., Noble, G., Cassidy, E.: A nationwide outbreak of Reye's Syndrome. Its epidemiologic relationship to Influenza B. Am. J. Med.61, 615–625 (1976).

    Google Scholar 

  8. Davison, A. M., Thomson, D., Robson, J. S.: Intravascular coagulation complicating Influenza A virus infection. Br. Med. J.1, 654–655 (1973).

    Google Scholar 

  9. Easterday, B. C., Tumova, B.: Avian Influenza Viruses: An avian specieses and natural history of Influenza. Advan. Vet. Sci. Comp. Med.16, 201–222 (1972).

    Google Scholar 

  10. Edelen, J. S., Bender, T. B., Chin, T. D. Y.: Encephalopathy and pericarditis during an outbreak of influenza. Am. J. Epidemiol.100, 79–84 (1974).

    Google Scholar 

  11. Flewett, T. H., Hoult, J. G.: Influenzal encephalopathy and post-influenzal encephalitis. Lancet2, 11–15 (1958).

    Google Scholar 

  12. Hall, W. W., Lamb, R. A., Choppin, P. W.: The polypeptides of canine distemper virus: synthesis in infected cells and relatedness to the polypeptides of other morbilliviruses. Virology100, 433–449 (1980).

    Google Scholar 

  13. Hamre, D., Appel, J., Loosli, C. G.: Viremia in mice with pulmonary influenza A virus infection. J. Lab. and Clin. Med.47, 182 (1956).

    Google Scholar 

  14. Hildebrandt, H. M., Maassab, H. F., Willis, P. W.: Influenza virus pericarditis. Am. J. Dis. Child.104, 179–182 (1962).

    Google Scholar 

  15. Homma, M., Ohuchi, M.: Trypsin action on the growth of Sendai virus in tissue culture cells. III. Structural difference of Sendai viruses grown in eggs and tissue culture cells. J. Virol.12, 1457–1465 (1973).

    Google Scholar 

  16. Huang, R. T. C., Wahn, K., Klenk, H.-D., Rott, R.: Fusion between cells membrane and liposomes containing the glycoproteins of influenza virus. Virology104, 294–302 (1980).

    Google Scholar 

  17. Huang, R. T. C., Rott, R., Klenk, H.-D.: Influenza viruses cause hemolysis and fusion of cells. Virology110, 243–247 (1981).

    Google Scholar 

  18. Kaji, M., Oseasohn, R., Jordan, W. S., Dingle, J. H.: Isolation of Asian virus from extrapulmonary tissues in fatal human influenza. Proc. Soc. Exper. and Med.100, 272–275 (1959).

    Google Scholar 

  19. Ketiladze, E. S., Knyazeva, L. D., Krylov, V. F., Litvin, L. L., Martyanova, E. M., Chekal, L. V.: Severe forms of Influenza and their treatment. Therapeutic Archive (U.S.S.R.)2, 123–126 (1978).

    Google Scholar 

  20. Klenk, H.-D., Rott, R., Orlich, M., Blödorn, J.: Activation of influenza viruses by trypsin treatment. Virology68, 426–439 (1975).

    Google Scholar 

  21. Klenk, H.-D., Rott, R., Orlich, M.: Further studies on the activation of influenza virus by proteolytic cleavage of the hemagglutinin. J. gen. Virol.36, 151–161 (1977).

    Google Scholar 

  22. Laver, W. G.: Separation of two polypeptides chains from the hemagglutinin subunit of influenza virus. Virology45, 275–278 (1971).

    Google Scholar 

  23. Lazarowitz, S. G., Goldberg, A. R., Choppin, P. W.: Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus. Host cell activation of serum plasminogen. Virology56, 172–180 (1973).

    Google Scholar 

  24. Lazarowitz, S. G., Choppin, P. W.: Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology68, 440–454 (1975).

    Google Scholar 

  25. Lehmann, N. J., Gust, J. D.: Viraemia in influenza a report of two cases. Med. J. Australia2, 1166–1169 (1971).

    Google Scholar 

  26. Lindsay, M. J., Herrmann, E. C., Morrow, G. W., Brown, A. L.: Hong Kong Influenza clinical, microbiologic, and pathologic features in 127 cases. Jama214, 1825–1832 (1970).

    Google Scholar 

  27. Louria, D. B., Blumenfeld, H. L., Elis, J. T., Kilbourne, E. D., Rogers, D. E.: Studies on influenza in the pandemic of 1957–1958. II. Pulmonary complications of Influenza. J. Clin. Invest.38, 213–274 (1959).

    Google Scholar 

  28. Lorand, L.: Introduction to clotting and lysis in blood plasma. Meth. Enzymol.45, 31–37 (1976).

    Google Scholar 

  29. Murphy, A. M., Hawkes, R. A.: Neurological complications of influenza A2/Hong Kong/68 virus. Med. J. Australia2, 511 (1970).

    Google Scholar 

  30. McKay, D. G., Margaretten, W.: Disseminated intravascular coagulation in virus diseases. Arch. Int. Med.120, 129–152 (1967).

    Google Scholar 

  31. Naficy, K.: Human influenza infection with proved viremia. N. Engl. J. Med.269, 964–966 (1963).

    Google Scholar 

  32. Nagai, Y., Klenk, H.-D., Rott, R.: Proteolytic cleavage of the viral glycoprotein sand its significance for the virulence of Newcastle disease virus. Virology72, 494–508 (1976).

    Google Scholar 

  33. Nakajima, K., Sugiura, A.: Neurovirulence of influenza virus in mice. II. Mechanism of virulence as studied in neurablastoma cell line. Virology101, 450–457 (1980).

    Google Scholar 

  34. Noble, R. L., Zillington, G. A., Kempson, R. L.: Fatal diffuse influenzal pneumonia: premorten diagnosis by lung biopsy. Chest63, 644–647 (1973).

    Google Scholar 

  35. Newton-John, H. F., Yung, A. P., Bennett, N. M., Forber, J. A.: Influenza virus pneumonitis a report of ten cases. Med. J. Australia2, 1160–1166 (1971).

    Google Scholar 

  36. Podlevsky, A. F., Belayeva, N. M., Zlydnikov, D. M.: Analysis of the causes of death due to A/England Influenza in Leningrad. Clin. Med. (U.S.S.R.)10, 118 to 121 (1975).

    Google Scholar 

  37. Polyakova, T. G., Keteladze, E. S., Zhilina, N. N., Stakhanova, V. M.: Study of viraemia in A2 Hong Kong Influenza. Voprosi Virusologii (U.S.S.R.)6, 724–728 (1970).

    Google Scholar 

  38. Ratnoff, O. D.: Some relationships among hemostasis, fibrinolytic phenomena, immunity and inflamantory process. Advan. Immunol.10, 145–227 (1969).

    Google Scholar 

  39. Rott, R., Reinacher, M., Orlich, M., Klenk, H.-D.: Cleavability of hemagglutinin determines spread of avian influenza viruses in the chorion allentoic membrane of chicken embryo. Arch. Virol.65, 123–135 (1980).

    Google Scholar 

  40. Scheid, A., Choppin, P. W.: 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. Virology57, 475–490 (1974).

    Google Scholar 

  41. Shenouda, A., Hatch, F. E.: Influenza A viral infection associated with acute renal failure. Am. J. Med.61, 697–702 (1976).

    Google Scholar 

  42. Skehel, J. J., Waterfield, M. D.: Studies on primary structure of the influenza virus hemagglutinin. Proc. Nat. Acad. Sci. U.S.A.72, 93–97 (1975).

    Google Scholar 

  43. Sugawara, K., Ohuchi, M., Nakamura, K., Homma, M.: Effects of various proteases on the glycoprotein composition and the infectivity in influenza C virus. Arch. Virol.68, 147–151 (1981).

    Google Scholar 

  44. Vallbracht, A., Scholtissek, C., Flehming, B., Gerth, H.-J.: Recombination of influenza A strains with fowl plaque virus can change pneumotropism for mice to a generalized infection with involvement of the central nervous system. Virology107, 452–460 (1980).

    Google Scholar 

  45. Wells, M. A., Albrecht, P., Ennis, F. A.: Recovery from a viral respiratory infection. I. Influenza pneumonia in normal and T deficient mice. J. Immunol.126, 1036–1041 (1981).

    Google Scholar 

  46. Wells, M. A., Ennis, F. A., Daniel, S.: Cytotoxic T-cell and antibody responses to influenza infection of mice. J. gen. Virol.43, 685–690 (1979).

    Google Scholar 

  47. Whitaker, A. N., Bunce, J., Graeme, E. R.: Disseminated intravascular coagulation and acute renal failure in influenza A2 infection. Med. J. Aust.2, 196–198 (1974).

    Google Scholar 

  48. Yap, K. L., Braciale, T. J., Ada, G. L.: Role of T-cell function in recovery from murine influenza infection. Cell. Immunol.43, 341–437 (1979).

    Google Scholar 

  49. Zakstelskaya, L. Y.: Recovery of virus from urine of patients with epidemic influenza, 72. Moscow 1953.

  50. Zhirnov, O. P., Ovcharenko, A. V., Bukrinskaya, A. G.: A modified plaque assay method for accurate analysis of infectivity of influenza viruses with uncleaved hemagglutinin. Arch. Virol.71, 177–183 (1982).

    Google Scholar 

  51. Zhirnov, O. P., Ovchurenko, A. V., Bukrinskaya, A. Y.: Proteolytic activation of the influenza WSN virus in cultured cells is performed by homologous plasma enzymes. J. gen. Virol. 1982 (in press).

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Authors and Affiliations

  1. The D.I. Ivanovsky Institute of Virology, the U.S.S.R. Academy of Medical Sciences, Moscow, USSR

    O. P. Zhirnov, A. V. Ovcharenko & A. G. Bukrinskaya

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  1. O. P. Zhirnov
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  2. A. V. Ovcharenko
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  3. A. G. Bukrinskaya
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Zhirnov, O.P., Ovcharenko, A.V. & Bukrinskaya, A.G. Protective effect of protease inhibitors in influenza virus infected animals. Archives of Virology 73, 263–272 (1982). https://doi.org/10.1007/BF01318080

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