1887

Abstract

Summary

The virulence of temperature-sensitive mutants of vesicular stomatitis virus (VSV) injected subcutaneously into newborn hamsters was positively correlated with their tendency to generate revertants and with their leakiness in cultured hamster embryo fibroblasts maintained at 37 °C, the measured body temperature of the animals under our experimental conditions. The complementation group of the mutants seemed important only in that it tended to determine reversion frequency and leakiness. One non-reverting group I mutant (T1026), however, was much less virulent than would be expected from its extreme eakiness at body temperature.

The disease produced by the less virulent mutants was characterized by neurological symptoms and led to delayed death, unlike the rapid death produced by virulent mutants. Infectious virus could be found in higher titres in the brains than in peripheral organs of such animals (with ratios as high as 10). This neurotropism was not correlated with the complementation group of themutant but was shown to be the consequence of survival for more than 3 days after injection. Age was not responsible for the effect. Animals injected at birth with T1026 were completely resistant to subcutaneous superinfection with the highly virulent wild-type virus HR at 3 to 4 days, though non-T1026-protected animals were completely sensitive. When HR was injected intracerebrally at 3 to 4 days, the T1026-protected animals allowed replication to high titres in the brain but not in peripheral organs, whereas non-T1026-protected animals allowed replication to high titres in both brain and in peripheral organs.

We suggest from these results that the observed neurotropism is produced by a resistance mechanism operative in peripheral organs but not in the brain; this resistance develops rapidly in newborn animals on exposure to virus and clears virus from the peripheral organs leaving it in the brain. It is possible that our effect represents a controlled and accelerated induction of the classical peripheral resistance of animals to various viruses which normally develops with age.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-29-3-281
1975-12-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/29/3/JV0290030281.html?itemId=/content/journal/jgv/10.1099/0022-1317-29-3-281&mimeType=html&fmt=ahah

References

  1. Clark H. F., Koprowski H. 1971; Isolation of temperature-sensitive conditional lethal mutants of ‘fixed’ rabies virus. Journal of Virology 7:295–300
    [Google Scholar]
  2. Doyle M., Holland J. J. 1973; Prophylaxis and immunization in mice by use of virus-free defective T particles to protect against intracerebral infection by vesicular stomatitis virus. Proceedings of the National Academy of Sciences of the United States of America 70:2105–2108
    [Google Scholar]
  3. Falke D., Rowe W. P. 1965; Die Erkrankung der Maus durch das Virus der Stomatitus Vesicularis. I. Die Ausbreitung des Virus in Abhangigkeit vom Alter der Maus. Archiv für diegesamte Virusforschung 17:549–559
    [Google Scholar]
  4. Farmilo A. J., Stanners C. P. 1972; Mutant of vesicular stomatitis virus which allows deoxyribonucleic acid synthesis and division in cells synthesizing viral ribonucleic acid. Journal of Virology 10:605–613
    [Google Scholar]
  5. Fields B. N. 1972; Genetic manipulation of reovirus – a model for modification of disease?. New England Journal of Medicine 287:1026–1033
    [Google Scholar]
  6. Flamand A. 1970; Etude genetique du virus de la stomatite vesiculaire: classement de mutants thermo-sensibles spontanes en groupes de complementation. Journal of General Virology 8:187–195
    [Google Scholar]
  7. Irsch M. S., Zisman B., Allison A. C. 1970; Macrophages and age-dependent resistance to herpes simplex virus in mice. Journal of Immunology 104:1160–1165
    [Google Scholar]
  8. Johnson R. T. 1964; The pathogenesis of herpes virus encephalitis. II. A cellular basis for the development of resistance with age. Journal of Experimental Medicine 120:359–374
    [Google Scholar]
  9. Marcus P. I., Sekellick M. J. 1975; Cell killing by viruses. II. Cell killing by vesicular stomatitis virus: a requirement for virion-derived transcription. Virology 63:176–190
    [Google Scholar]
  10. Prinole C. R. 1970; Genetic characteristics of conditional lethal mutants of vesicular stomatitis virus induced by 5-fluorouracil, 5-azacytidine and ethyl methane sulfonate. Journal of Virology 5:559–567
    [Google Scholar]
  11. Sabin A. B., Olitsky P. K. 1938; Influence of host factors on neuro-invasiveness of vesicular stomatitis virus. III. Effect of age and pathway of infection on the character and localization of lesions in the central nervous system. Journal of Experimental Medicine 67:201–228
    [Google Scholar]
  12. Schincariol A. L., Howatson A. F. 1970; Replication of vesicular stomatitis virus. I. Viral specific RNA and nucleoprotein in infected L cells. Virology 42:732–743
    [Google Scholar]
  13. Stanners C. P., Farmilo A. J., Goldberg V. J. 1975; Effects in vitro and in vivo of a mutant of vesicular stomatitis virus with attenuated cytopathogenicity. In Negative Strand Viruses pp 785–798 Edited by Mahy B. W. J., Barry R. D. Cambridge: Academic Press;
    [Google Scholar]
  14. Stanners C. P., Eliceiri G. L., Green K. 1971; Two types of ribosomes in mouse-hamster hybrid cells. Nature New Biology 230:52–54
    [Google Scholar]
  15. Szilagyi J. F., Pringle C. R. 1972; Effect of temperature-sensitive mutations on the virion-associated RNA transcriptase of vesicular stomatitis virus. Journal of Molecular Biology 71:281–291
    [Google Scholar]
  16. Teisner B., Haake S. 1974; Poikilothermia and susceptibility of suckling mice to Coxsackie Bi virus. Nature, London 247:568
    [Google Scholar]
  17. Wagner R. R. 1974; Pathogenicity and immunogenicity for mice of temperature-sensitive mutants of vesicular stomatitis virus. Infection and Immunity 10:309–315
    [Google Scholar]
  18. Wong P. K. Y., Holloway A. F., Cormack D. V. 1972; Characterization of three complementation groups of vesicular stomatitis virus. Virology 50:829–840
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-29-3-281
Loading
/content/journal/jgv/10.1099/0022-1317-29-3-281
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error