Protection of Mice Infected with a Lethal Dose of Semliki Forest Virus by Defective Interfering Virus: Modulation of Virus Multiplication Free

Abstract

SUMMARY

Certain defective interfering (DI) Semliki Forest virus (SFV) preparations completely protected the majority of mice inoculated with a normally lethal dose of SFV, and the surviving mice showed no signs of disease during the period of observation. Depending upon which DI SFV preparation was used, the survivors were resistant to challenge with 100 LD SFV (DI SFV p13a), or were completely sensitive (DI SFV p4), the latter having evidently failed to establish a protective immunity. In this report we compared the ability of these two DI SFV preparations to inhibit multiplication of infectious virus in mice inoculated with 10 LD SFV. The following conclusions emerged: (i) virus multiplication was profoundly inhibited in the majority of mice treated with either of the DI virus preparations although there was significant multiplication in most tissues, including brain. The number of mice showing evidence of reduced infectivity titres (58%) correlated well with the 60% which survived without disease in lethality experiments. (ii) Despite the presence of infectivity, no SFV antigen or histopathological lesions were detected in brain or spinal cord. (iii) The DI virus preparations p4 and p13a altered the distribution of infectivity in the mouse in different ways: during the first 2 days of the infection modulated by DI virus p4, the infectivity titres (in brain, olfactory lobes and spleen) were comparatively high, being >1% of those in mice inoculated with standard virus alone. However, from day 3, titres declined precipitously and there was little infectivity in any of the tissues investigated. On the other hand, mice treated with DI SFV p13a had, over the entire duration of infection, greatly reduced though significant infectivity in brain, olfactory lobes and spleen and very little infectivity in serum. (iv) In a minority of mice (14.5%), DI virus p13a altered the distribution of infectivity between different tissues so that there was significantly decreased virus in just one or two of the four tissues investigated, suggesting that the infection was being subtly modulated by the DI virus. (v) Interference assays failed to detect DI SFV in any tissue samples although the effects of DI virus on infection in the mouse were obvious.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-65-11-1909
1984-11-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/65/11/JV0650111909.html?itemId=/content/journal/jgv/10.1099/0022-1317-65-11-1909&mimeType=html&fmt=ahah

References

  1. Barrett A. D. T., Dimmock N. J. 1984a; Variation in homotypic and heterotypic interference by defective interfering viruses derived from different strains of Semliki Forest virus and from Sindbis virus. Journal of General Virology 65:1119–1122
    [Google Scholar]
  2. Barrett A. D. T., Dimmock N. J. 1984b; Properties of host and virus which influence defective interfering virus-mediated protection of mice against Semliki Forest virus lethal encephalitis. Archives of Virology 91:185–188
    [Google Scholar]
  3. Barrett A. D. T., Dimmock N. J. 1984c; Modulation of Semliki Forest virus-induced infection of mice by defective interfering virus. Journal of Infectious Diseases 150:98–104
    [Google Scholar]
  4. Barrett A. D. T., Crouch C. F., Dimmock N. J. 1981; Assay of defective-interfering Semliki Forest virus by the inhibition of synthesis of virus-specified RNAs. Journal of General Virology 54:273–280
    [Google Scholar]
  5. Barrett A. D. T., Crouch C. F., Dimmock N. J. 1984; Defective interfering Semliki Forest virus populations are biologically and physically heterogeneous. Journal of General Virology 65:1273–1283
    [Google Scholar]
  6. Bellett A. J. D., Cooper P. D. 1959; Some properties of the transmissible interfering component of vesicular stomatitis virus preparations. Journal of General Microbiology 21:498–509
    [Google Scholar]
  7. Bradish C. J., Allner K., Maber H. B. 1971; The virulence of original and derived strains of Semliki Forest virus for mice, guinea-pigs and rabbits. Journal of General Virology 12:141–160
    [Google Scholar]
  8. Clarke D. H., Casals J. 1958; Techniques for hemagglutination and hemagglutination inhibition with arthropod-borne viruses. American Journal of Tropical Medicine and Hygiene 7:561–573
    [Google Scholar]
  9. Crouch C. F., Mackenzie A., Dimmock N. J. 1982; The effect of defective interfering Semliki Forest virus on the histopathology of infection with virulent Semliki Forest virus in mice. Journal of Infectious Diseases 146:411–416
    [Google Scholar]
  10. Dimmock N. J., Kennedy S. I. T. 1978; Prevention of death in Semliki Forest virus-infected mice by administration of defective-interfering Semliki Forest virus. Journal of General Virology 39:231–242
    [Google Scholar]
  11. Doyle M., Holland J. J. 1973; Prophylaxis and immunisation in mice by use of virus-free defective T particles to protect intracerebral infection by vesicular stomatitis virus. Proceedings of the National Academy of Sciences, U. S. A 70:2105–2108
    [Google Scholar]
  12. Fultz P. N., Shadduck J. A., Kang C.-Y., Streilein J. W. 1982; Vesicular stomatitis virus can establish persistent infections in Syrian hamsters. Journal of General Virology 63:493–497
    [Google Scholar]
  13. Holland J. J., Villareal L. P. 1975; Purification of defective interfering T particles of vesicular stomatitis and rabies viruses generated in vivo in brains of newborn mice. Virology 67:438–449
    [Google Scholar]
  14. Holland J. J., Kennedy S. I. T., Semler B. L., Jones C. L., Roux L., Grabau E. A. 1980; Defective interfering RNA viruses and the host cell response. In Comprehensive Virology vol 16: pp 137–192 Edited by Fraenkel-Conrat H., Wagner R. R. New York: Plenum Press;
    [Google Scholar]
  15. Huang A. S., Baltimore D. 1970; Defective viral particles and viral disease processes. Nature, London 226:325–327
    [Google Scholar]
  16. Huang A. S., Baltimore D. 1977; Defective interfering animal viruses. In Comprehensive Virology vol 10: pp 73–116 Edited by Fraenkel-Conrat H., Wagner R. R. New York: Plenum Press;
    [Google Scholar]
  17. Jones C. L., Holland J. J. 1980; Requirements for DI particle prophylaxis against vesicular stomatitis virus infection in vivo. Journal of General Virology 49:215–220
    [Google Scholar]
  18. Kӓӓriӓinen L., Pettersson R. F., Kerӓnen S., Lehtovaara P., Sӧderlund H., Ukkonen P. 1981; Multiple structurally related defective interfering RNAs formed during undiluted passages of Semliki Forest virus. Virology 113:686–697
    [Google Scholar]
  19. Kennedy S. I. T., Burke D. C. 1972; Studies on the structural and biological properties of Semliki Forest virus. Journal of General Virology 14:87–98
    [Google Scholar]
  20. Kowal K. J., Stollar V. 1980; Differential sensitivity of infectious and defective interfering particles of Sind-bis virus to ultraviolet irradiation. Virology 103:149–157
    [Google Scholar]
  21. Lazzarini R. A., Keene J. D., Schubert M. 1981; The origins of defective interfering particles of the negative-strand RNA viruses. Cell 26:145–154
    [Google Scholar]
  22. Lehtovaara P., Soderlund H., Kerӓnen S., Pettersson R. F., Kӓӓriӓinen L. 1981; 18S defective interfering RNA of Semliki Forest virus contains a triplicated linear repeat. Proceedings of the National Academy of Sciences, U. S. A 78:5353–5357
    [Google Scholar]
  23. Lehtovaara P., Sӧderlund H., Kerӓnen S., Pettersson R. F., Kӓӓriӓinen L. 1982; Extreme ends of thegenome are conserved and rearranged in the defective interfering RNAs of Semliki Forest virus. Journal of Molecular Biology 156:731–748
    [Google Scholar]
  24. Morser M. J., Kennedy S. I. T., Burke D. C. 1973; Virus-specified polypeptides in cells infected with Semliki Forest virus. Journal of General Virology 21:19–29
    [Google Scholar]
  25. Perrault J. 1981; Origins and replication of defective interfering particles. Current Topics in Microbiology and Immunology 93:151–207
    [Google Scholar]
  26. Pettersson R. F. 1981; 5′-terminal nucleotide sequence of Semliki Forest virus 18S defective interfering RNA is heterogeneous and different from the genomic 42S RNA. Proceedings of the National Academy of Sciences, U. S. A 78:115–119
    [Google Scholar]
  27. Prevec L., Kang C. Y. 1970; Homotypic and heterotypic interference by defective particles of vesicular stomatitis virus. Nature, London 228:25–27
    [Google Scholar]
  28. Rabinowitz S. G., Huprikar J. 1979; The influence of defective interfering particles of the PR-8 strain of influenza A virus on the pathogenesis of pulmonary infection of mice. Journal of Infectious Diseases 140:305–315
    [Google Scholar]
  29. Rabinowitz S. G., Dal Canto M. C., Johnson T. C. 1977; Infection of the central nervous system produced by mixtures of defective-interfering particles and wildtype vesicular stomatitis virus in mice. Journal of Infectious Diseases 136:59–74
    [Google Scholar]
  30. Schnitzlein W. M., Reichmann M. E. 1976; The size and cistronic origin of defective vesicular stomatitis virus particle RNAs in relation to homotypic and heterotypic interference. Journal of Molecular Biology 101:307–325
    [Google Scholar]
  31. Sӧderlund H., Kerӓnen S., Lehtovaara P., Palva I., Pettersson R. F., Kӓӓriӓinen L. 1981; Structural Complexity of defective interfering RNAs of Semliki Forest virus as revealed by analysis of complementary DNA. Nucleic Acids Research 9:3403–3417
    [Google Scholar]
  32. Spandidos D. A., Graham A. F. 1976; Generation of defective virus after infection of newborn rats with reovirus. Journal of Virology 20:234–247
    [Google Scholar]
  33. Von Magnus P. 1951; Propagation of the PR8 strain of influenza A virus in chick embryos. III. Properties of the incomplete virus produced in several passages of undiluted virus. Acta pathologica el microbiologica scandinavica 29:157–181
    [Google Scholar]
  34. Welsh R. M., Lampert P. W., Oldstone M. B. A. 1977; Prevention of virus-induced cerebellar disease by defective interfering lymphocytic choriomeningitis virus. Journal of Infectious Diseases 136:391–399
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-65-11-1909
Loading
/content/journal/jgv/10.1099/0022-1317-65-11-1909
Loading

Data & Media loading...

Most cited Most Cited RSS feed