1887

Abstract

Summary

To study the pathogenicity of murine cytomegalovirus (MCMV) and to identify virulence determinants, we have isolated and phenotypically characterized a set of temperature-sensitive mutants. One mutant, PP269/38, was avirulent for 1-week-old BALB/c mice and restricted in its plaque formation and replication at 39 °C. Mutants PP242/68 and PP268/38 were 100-fold less virulent than salivary gland-grown virus (SGV), even after two passages in the salivary glands of 1-week-old mice. The former mutant was unable to replicate or form plaques at 39 °C whereas the latter replicated poorly at 39 °C but not at all at 40 °C although it was able to form plaques at 40 °C with a reduced plaque size. PP31/15 exhibited a 40-fold reduction in virulence compared to SGV after two passages and was unable to form plaques or to replicate at 40 °C; at 39 °C it was able to, with reduced efficiency. The remaining two mutants, PP99/3 and PP392/31, were 10-fold less virulent than SGV and were restricted at 40 °C. The six mutants have been classified into at least four complementation groups. These mutants may be useful for studying various aspects of MCMV pathogenicity.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-70-9-2373
1989-09-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/70/9/JV0700092373.html?itemId=/content/journal/jgv/10.1099/0022-1317-70-9-2373&mimeType=html&fmt=ahah

References

  1. Alford A. M., Brut W. J. 1985; Cytomegalovirus. In Virology629–660 Fields B. N., Knipe D. M., Chanock R. M., Melnick J., Roizman B., Shope R. E. New York: Raven Press;
    [Google Scholar]
  2. Chong K. T., Gould J. I., Mims C. A. 1981; Neutralization of different strains of murine cytomegalovirus (MCMV) - effect of in vitro passage. Archives of Virology 69:95–104
    [Google Scholar]
  3. Dion M., Hamelin C. 1987; Isolation and preliminary characterization of temperature-sensitive mutants of human cytomegalovirus. Virology 158:228–230
    [Google Scholar]
  4. Eizura Y., Minamishima Y. 1979; Co-variation of pathogenicity and antigenicity in murine cytomegalovirus. Microbiology and Immunology 23:559–564
    [Google Scholar]
  5. Glenn J. 1981; Cytomegalovirus infections following renal transplantation. Reviews of Infectious Diseases 3:1151–1178
    [Google Scholar]
  6. Griffith B. P., McCormick S. R., Fong C. K. Y., Lavallee J. T., Lucia H. L., Goff E. 1985; The placenta as a site of cytomegalovirus infection in guinea pigs. Journal of Virology 55:404–409
    [Google Scholar]
  7. Griffiths P. D., Grundy J. E. 1987; Molecular biology and immunology of cytomegalovirus. Biochemical Journal 241:313–324
    [Google Scholar]
  8. Griffiths P. D., Grundy J. E. 1988; The status of CMV as a human pathogen. Epidemiology and Infection 100:1–15
    [Google Scholar]
  9. Hudson J. B. 1979; The murine cytomegalovirus as a model for the study of viral pathogenesis and persistent infections. Archives of Virology 62:1–29
    [Google Scholar]
  10. Hudson I. B., Misra V., Mosmann T. R. 1976a; Properties of the multicapsid virions of murine cytomegalovirus. Virology 72:224–234
    [Google Scholar]
  11. Hudson J. B., Misra V., Mosmann T. R. 1976b; Cytomegalovirus infectivity: analysis of the phenomenon of centrifugal enhancement of infectivity. Virology 72:235–243
    [Google Scholar]
  12. Inada T., Mims C. A. 1985; Association of virulence of murine cytomegalovirus with macrophage susceptibility and with virion-bound non-neutralizing antibody. Journal of General Virology 66:879–882
    [Google Scholar]
  13. Inada T., Chong K. T., Mims C. A. 1985; Enhancing antibodies, macrophages and virulence in mouse cytomegalovirus infection. Journal of General Virology 66:871–878
    [Google Scholar]
  14. Jordan M. C., Takagi J. L. 1983; Virulence characteristics of murine cytomegalovirus in cell and organ cultures. Infection and Immunity 41:841–843
    [Google Scholar]
  15. Macher A. M., Reichart C M., Straus S. E., Longo D. L., Parrillo J., Lane C., Fauci A. S., Hook A. H., Manischewitz I. F., Quinnan G. V. 1983; Death in the AIDS patient: role of cytomegalovirus. New England Journal of Medicine 309:1454
    [Google Scholar]
  16. Meijer H., Dreesen J. C. F. M., Van boven C. P. A. 1986; Molecular cloning and restriction endonuclease mapping of the rat cytomegalovirus genome. Journal of General Virology 67:1327–1342
    [Google Scholar]
  17. Mims C. A., Gould J. 1979; Infection of salivary glands, kidneys, adrenals, ovaries and epithelia by murine cytomegalovirus. Journal of Medical Microbiology 12:113–122
    [Google Scholar]
  18. Osborn J. E. 1982; Cytomegalovirus and other herpesviruses. In The Mouse in Biomedical Research 2267–292 Foster H. L., Small J. D., Fox J. G. New York & London: Academic Press;
    [Google Scholar]
  19. Osborn J. E., Walker D. L. 1968; Enhancement of infectivity of murine cytomegalovirus in vitro by centrifugal inoculation. Journal of Virology 2:853–858
    [Google Scholar]
  20. Osborn J. E., Walker D. L. 1971; Virulence and attenuation of murine cytomegalovirus. Infection and Immunity 3:228–326
    [Google Scholar]
  21. Quinnan G. V., Manischewitz I. F. 1987; Genetically determined resistance to lethal murine cytomegalovirus is mediated by interferon-dependent and -independent restriction of virus replication. Journal of Virology 61:1875–1881
    [Google Scholar]
  22. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. American Journal of Hygiene 27:493–497
    [Google Scholar]
  23. Rosenwirth B., Ziegenhagen D., Eggers H. J. 1988; Biochemistry and pathogenicity of echovirus 9. III. Thermosensitive mutants of echovirus 9, strain Barty, with reduced pathogenicity for newborn mice. Medical Microbiology and Immunology 177:69–81
    [Google Scholar]
  24. Sandford G. R., Burns W. H. 1988; Use of temperature-sensitive mutants of mouse cytomegalovirus as vaccines. Journal of Infectious Diseases 158:596–601
    [Google Scholar]
  25. Sandford G. R., Wingard J. R., Simons J. W., Staal S. P., Saral R., Burns W. H. 1985; Genetic analysis of the susceptibility of mouse cytomegalovirus to acyclovir. Journal of Virology 54:104–113
    [Google Scholar]
  26. Selgrade M. K., Nedrud J. G., Collier A. M., Gardner D. E. 1981; Effect of cell source, mouse strain and immunosuppressive treatment on production of virulent and attenuated murine cytomegalovirus. Infection and Immunity 33:840–847
    [Google Scholar]
  27. Shellam G. R., Flexman J. P. 1986; Genetically determined resistance to murine cytomegalovirus and herpes simplex virus in newborn mice. Journal of Virology 58:152–156
    [Google Scholar]
  28. Shellam G. R., Grundy J. E., Harnett G. B., Allen I. E. 1983; Natural resistance against cytomegalovirus and other viruses in mice. Progress in Immunology 5:1209–1217
    [Google Scholar]
  29. Sweet C., Toms G. L., Smith H. 1977; The pregnant ferret as a model for studying the congenital effects of influenza infection in utero: infection of foetal tissues in organ culture and in vivo. British Journal of Experimental Pathology 58:113–123
    [Google Scholar]
  30. Tonari Y., Minamishjma Y. 1983; Pathogenicity and immunogenicity of temperature-sensitive mutants of mouse cytomegalovirus. Journal of General Virology 64:1983–1990
    [Google Scholar]
  31. Weiland F., Keil G. M., Reddehase M. J., Koszinowski U. H. 1986; Studies on the morphogenesis of murine cytomegalovirus. Intervirology 26:192–201
    [Google Scholar]
  32. Wicker R., Gunther M. 1988; Isolation and characterization of thermosensitive mutants from Kilham rat virus, a rodent parvovirus. Journal of General Virology 69:163–175
    [Google Scholar]
  33. Yamanishi K., Rapp F. 1977; Temperature-sensitive mutants of human cytomegalovirus. Journal of Virology 24:416–18
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-70-9-2373
Loading
/content/journal/jgv/10.1099/0022-1317-70-9-2373
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