1887

Abstract

Summary

Infant rats were infected intranasally with wild influenza virus strains, attenuated strain A/Okuda/57 or recombinants prepared from these parents. The growth of viruses in the turbinates or lungs, and the ability of virus infections to potentiate subsequent bacterial infection by (HIb) were measured. The two wild strains of virus and a recombinant strain WRL105, known to be virulent for man, reached titres of 10 − 10 EBID50/ml in the turbinates of infant rats 48 h after infection; infection by these viruses was followed by HIb bacteraemia in 77-92% and meningitis in 58-75% of animals. In contrast, virus strains known to be attenuated for man grew to lower titres in infant-rat turbinates and promoted a lower incidence of systemic infection by HIb than the virulent strains. A comparison of the various results of infection of infant rats with influenza virus strains of known pathogenicity for man indicated that the subsequent incidence of HIb bacteraemia was the most discriminating measurement of virus virulence; the range of yields of attenuated virus in rat turbinates overlapped that of virulent strains. These results, together with those of previous studies, indicate that the behaviour of influenza viruses in infant rats is an indication of virus virulence for man, and could provide a test of virulence that would facilitate the development of live attenuated virus vaccines for human use.

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/content/journal/jmm/10.1099/00222615-13-2-297
1980-05-01
2024-04-26
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References

  1. Almond J. W. 1977; A single gene determines the host range of influenza virus. Nature 270:617
    [Google Scholar]
  2. Bean W. J., Webster R. G. 1978; Phenotypic properties associated with influenza genome segments. In Negative strand viruses and the host cell edited by Mahy B.W.J., Barry R.D. Academic Press; London: p 685
    [Google Scholar]
  3. Beare A. S., Hall T. S. 1971; Recombinant influenza A viruses as live vaccines for man. Lancet 2:1271
    [Google Scholar]
  4. Campbell D., Sweet C., Smith H. 1979; Comparisons of virulence of influenza virus recombinants in ferrets in relation to their behaviour in man and their genetic constitution. J. gen. Virol 44:37
    [Google Scholar]
  5. Fazekas de St Groth S., Withell J., Lafferty K. J. 1958; An improved assay method for neutralizing antibodies against influenza viruses. J. Hyg., Camb 56:415
    [Google Scholar]
  6. Fell P. J., Watson N. P., O’Donnell H. J., Simmons R. L., Hasell S. K. 1977; Longer term effects of live influenza vaccine in patients with chronic pulmonary disease. Lancet 1:1282
    [Google Scholar]
  7. Fenton R. J., Jennings R., Potter C. W. 1977; Differential response of ferrets to infection with virulent and avirulent influenza viruses: a possible marker of virus attenuation. Archs Virol 55:55
    [Google Scholar]
  8. Freestone D. S., Bowker C. H., Letley E., Ferris R. D., White W. G., Barnes G. M. 1976; A clinical trial of WRL105 strain live attenuated influenza vaccine comparing four methods of intranasal vaccination. J. Hyg., Camb 76:459
    [Google Scholar]
  9. Hara K., Beare A. S., Tyrrell D. A. J. 1974; Growth and pathogenicity of influenza viruses in organ cultures of ciliated epithelium. Arch. ges. Virusforsch 44:227
    [Google Scholar]
  10. Hay A. J., Bellamy A. R., Abraham G., Skehel J. J., Brand C. M., Webster R. G. 1977; Procedures for the characterization of the genetic material of candidate vaccine strains. Dev. biol. Stand 39:15
    [Google Scholar]
  11. Lobmann M., Delem A., Peetermans J., Huygelen C. 1976; Laboratory characteristics of an attenuated influenza type A (H3N2) virus (“Alice” strain). J. Hyg., Camb 77:181
    [Google Scholar]
  12. McCahon D., Beare A. S., Stealey V. 1976; The production of live attenuated influenza A strains by recombination with A/Okuda/57 H2N2). Postgrad, med. J 5:389
    [Google Scholar]
  13. Mahmud M. I. A., Jennings R., Potter C. W. 1979a; The infant rat as a model for the assessment of attenuation of human influenza viruses. J. med. Microbiol 12:43
    [Google Scholar]
  14. Mahmud M. I. A., Maassab H. F., Jennings R., Potter C. W. 1979b; Influenza virus infection in newborn rats: virulence of recombinant strains prepared from a cold-adapted, attenuated parent. Archs Virol 61:207
    [Google Scholar]
  15. Michaels R. H., Mahmud M. I. A., Coup A. J., Jennings R., Potter C. W. 1978; Influenza virus infection in newborn rats: a possible marker of attenuation for man. J. med. Virol 2:253
    [Google Scholar]
  16. Moffat M. A. J., Stealey V. M., Freestone D. S., MacDonald A. 1976; Assessment of elicited antibody responses, clinical reactions and transmissiblity of WRL105 live influenza vaccine. J. biol. Stand 4:91
    [Google Scholar]
  17. Morris C. A., Freestone D. S., Stealey V. M., Oliver P. R. 1975; Recombinant WRL105 strain live attenuated influenza vaccine. Immunogenicity, reactivity and transmissibility. Lancet 2:196
    [Google Scholar]
  18. Mostow S. R., Tyrrell D. A. J. 1972; Detection of attenuation of recombinant influenza viruses in vitro. Lancet 2:116
    [Google Scholar]
  19. Mostow S. R., Tyrrell D. A. J. 1973; The behaviour in vitro of attenuated recombinant influenza viruses. Arch. ges. Virusforsch 43:385
    [Google Scholar]
  20. Murphy B. R., Chalhub E. G., Nusinoff S. R., Chanock R. M. 1972; Temperature-sensitive mutants of influenza virus. II. Attenuation of ts recombinants for man. J. inf. Dis 126:170
    [Google Scholar]
  21. Okuno Y., Nakamura K. 1966; Prophylactic effectiveness of live influenza vaccine in 1965. Biken J 9:89
    [Google Scholar]
  22. Oxford J. S., McGeoch D. J., Schild G. C., Beare A. S. 1978; Analysis of virion RNA segments and polypeptides of influenza A virus recombinants of defined virulence. Nature, Lond 273:778
    [Google Scholar]
  23. Reed L. J., Muench H. 1938; A simple method of estimating fifty per cent endpoints. Am. J. Hyg 27:493
    [Google Scholar]
  24. Rott R., Orlich M., Scholtissek C. 1976; Attenuation of pathogenicity of fowl plague virus by recombination with other influenza A viruses non-pathogenic for fowl: non exclusive dependence of pathogenicity on hemagglutinin and neuraminidase of the virus. J. Virol 19:54
    [Google Scholar]
  25. Toms G. L., Bird R. A., Kingsman S. M., Sweet C., Smith H. 1976; The behaviour in ferrets of two closely related clones of influenza virus of differing virulence for man. Br. J. exp. Path 57:37
    [Google Scholar]
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