Abstract
The virulence in neonatal mice of temperature-sensitive (ts) mutants of Sindbis virus was determined by measurements of mean survival time and 50% lethal dose after intracerebral injection. For 11 ts mutants, mean survival time was determined by the ribonucleic acid (RNA) phenotype, RNA+ mutants killing the mice sooner than RNA- mutants for the same titer of virus injected. Mortality caused by seven ts mutants was, with one exception, correlated with the proportion of revertants recovered after death. A82, a presumed double mutant showing low reversion, showed no detectable lethality. The pathogenicity of this mutant could be detected by inhibition of weight gain, which was proportional to the titer of virus injected. A low-level persistence, independent of the titer injected, occurred up to 7 days after injection. This was followed by complete clearance. It is concluded that the virulence of Sindbis virus may be considerably altered by mutation, and that this is related to events occurring at the cellular level.
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Selected References
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- Atkins G. J., Johnston M. D., Westmacott L. M., Burke D. C. Department of Biological Sciences, University of Warwick, Coventry, CV47AL, England. J Gen Virol. 1974 Dec;25(3):381–390. doi: 10.1099/0022-1317-25-3-381. [DOI] [PubMed] [Google Scholar]
- Atkins G. J., Lancashire C. L. The induction of interferon by temperature-sensitive mutants of Sindbis virus: its relationship to double-stranded RNA synthesis and cytopathic effect. J Gen Virol. 1976 Feb;30(2):157–165. doi: 10.1099/0022-1317-30-2-157. [DOI] [PubMed] [Google Scholar]
- Atkins G. J., Samuels J., Kennedy S. I. Isolation and preliminary characterization of temperature-sensitive mutants of Sindbis virus strain AR339. J Gen Virol. 1974 Dec;25(3):371–380. doi: 10.1099/0022-1317-25-3-371. [DOI] [PubMed] [Google Scholar]
- Atkins G. J. The effect of infection with Sindbis virus and its temperature-sensitive mutants on cellular protein and DNA synthesis. Virology. 1976 Jun;71(2):593–597. doi: 10.1016/0042-6822(76)90384-6. [DOI] [PubMed] [Google Scholar]
- Brzeski H., Clegg J. C., Atkins G. J., Kennedy S. I. Regulation of the synthesis of Sindbis virus-specified RNA: role of the virion core protein. J Gen Virol. 1978 Mar;38(3):461–470. doi: 10.1099/0022-1317-38-3-461. [DOI] [PubMed] [Google Scholar]
- Haspel M. V., Duff R., Rapp F. Experimental measles encephalitis: a genetic analysis. Infect Immun. 1975 Oct;12(4):785–790. doi: 10.1128/iai.12.4.785-790.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preble O. T., Youngner J. S. Temperature-sensitive viruses and the etiology of chronic and inapparent infections. J Infect Dis. 1975 Apr;131(4):467–473. doi: 10.1093/infdis/131.4.467. [DOI] [PubMed] [Google Scholar]
- Rabinowitz S. G., Dal Canto M. C., Johnson T. C. Comparison of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus. Infect Immun. 1976 Apr;13(4):1242–1249. doi: 10.1128/iai.13.4.1242-1249.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabinowitz S. G., Johnson T. C., Dal Canto M. C. The uncoupled relationship between the temperature-sensitivity and neurovirulence in mice of mutants of vesicular stomatitis virus. J Gen Virol. 1977 May;35(2):237–249. doi: 10.1099/0022-1317-35-2-237. [DOI] [PubMed] [Google Scholar]
- Richmond J. Y. Evidence for a mouse pathogenicity locus in certain temperature-sensitive mutants of foot-and-mouth disease virus. Infect Immun. 1977 Jun;16(3):827–831. doi: 10.1128/iai.16.3.827-831.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schluter B., Bellomy B., Brown A. Pathogenesis of temperature-sensitive mutants of sindbis virus in the embryonated egg. I. Characterization and kinetics of viral multiplication. Infect Immun. 1974 Jan;9(1):68–75. doi: 10.1128/iai.9.1.68-75.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanners C. P., Goldberg V. J. On the mechanism of neurotropism of vesicular stomatitis virus in newborn hamsters. Studies with temperature-sensitive mutants. J Gen Virol. 1975 Dec;29(3):281–296. doi: 10.1099/0022-1317-29-3-281. [DOI] [PubMed] [Google Scholar]
- Tarr G. C., Lubiniecki A. S. Chemically induced temperature-sensitive mutants of dengue virus type 2: comparison of temperature sensitivity in vitro with infectivity suckling mice, hamsters, and rhesus monkeys. Infect Immun. 1976 Mar;13(3):688–695. doi: 10.1128/iai.13.3.688-695.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]