Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1981 Sep;33(3):840–847. doi: 10.1128/iai.33.3.840-847.1981

Effects of cell source, mouse strain, and immunosuppressive treatment on production of virulent and attenuated murine cytomegalovirus.

M K Selgrade, J G Nedrud, A M Collier, D E Gardner
PMCID: PMC350788  PMID: 6270000

Abstract

Murine cytomegalovirus pools from various in vitro and in vivo sources were compared for virulence in suckling mice in an effort to identify the conditions which were necessary for the production of virulent and attenuated viruses. Virus passaged in tracheal ring and salivary gland organ cultures, where virus is produced primarily by epithelial cells, was even more attenuated than virus passaged in mouse embryo fibroblasts. The attenuation observed after passage in all three of these in vitro systems did not appear to be due to defective interfering particles. We also found that virus produced in vivo in salivary glands became attenuated with time after infection. Virus harvested from salivary glands 5 to 6 weeks after infection was highly attenuated compared with both salivary gland-passaged virus harvested 2 to 3 weeks after infection and tissue culture-passaged virus. The attenuation of salivary gland-passaged virus with time was reversed when animals were treated with cyclophosphamide before the virus was harvested. A comparison of virus pools harvested from susceptible and resistant mouse strains indicated that the mouse strain had little effect on the virulence of the virus produced. When the various sources of virus tested in this study were ranked in terms of the virulence of the virus produced, salivary glands in intact mice either 2 to 3 weeks after infection or after cyclophosphamide treatment produced the most virulent virus, followed by mouse embryo fibroblast cultures, tracheal ring and salivary gland organ cultures, and, finally, salivary glands in intact mice 5 to 6 weeks after infection.

Full text

PDF
840

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chalmer J. E., Mackenzie J. S., Stanley N. F. Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse. J Gen Virol. 1977 Oct;37(1):107–114. doi: 10.1099/0022-1317-37-1-107. [DOI] [PubMed] [Google Scholar]
  2. Eizuru Y., Minamishima Y. Co-variation of pathogenicity and antigenicity in murine cytomegalovirus. Microbiol Immunol. 1979;23(6):559–564. doi: 10.1111/j.1348-0421.1979.tb00496.x. [DOI] [PubMed] [Google Scholar]
  3. Elek S. D., Stern H. Development of a vaccine against mental retardation caused by cytomegalovirus infection in utero. Lancet. 1974 Jan 5;1(7845):1–5. doi: 10.1016/s0140-6736(74)92997-3. [DOI] [PubMed] [Google Scholar]
  4. Fiala M., Payne J. E., Berne T. V., Moore T. C., Henle W., Montgomerie J. Z., Chatterjee S. N., Guze L. B. Epidemiology of cytomegalovirus infection after transplantation and immunosuppression. J Infect Dis. 1975 Oct;132(4):421–433. doi: 10.1093/infdis/132.4.421. [DOI] [PubMed] [Google Scholar]
  5. Hanshaw J. B. Congenital cytomegalovirus infection: a fifteen year perspective. J Infect Dis. 1971 May;123(5):555–561. doi: 10.1093/infdis/123.5.555. [DOI] [PubMed] [Google Scholar]
  6. Howard R. J., Balfour H. H., Jr Prevention of morbidity and mortality of wild murine cytomegalovirus by vaccination with attenuated cytomegalovirus. Proc Soc Exp Biol Med. 1977 Nov;156(2):365–368. doi: 10.3181/00379727-156-39937. [DOI] [PubMed] [Google Scholar]
  7. Hudson J. B., Misra V., Mosmann T. R. Properties of the multicapsid virions of murine cytomegalovirus. Virology. 1976 Jul 1;72(1):224–234. doi: 10.1016/0042-6822(76)90325-1. [DOI] [PubMed] [Google Scholar]
  8. Jordan M. C. Adverse effects of cytomegalovirus vaccination in mice. J Clin Invest. 1980 Apr;65(4):798–803. doi: 10.1172/JCI109730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jordan M. C., Shanley J. D., Stevens J. G. Immunosuppression reactivates and disseminates latent murine cytomegalovirus. J Gen Virol. 1977 Nov;37(2):419–423. doi: 10.1099/0022-1317-37-2-419. [DOI] [PubMed] [Google Scholar]
  10. Lopez C., Simmons R. L., Mauer S. M., Najarian J. S., Good R. A., Gentry S. Association of renal allograft rejection with virus infections. Am J Med. 1974 Mar;56(3):280–289. doi: 10.1016/0002-9343(74)90609-3. [DOI] [PubMed] [Google Scholar]
  11. Mayo D., Armstrong J. A., Ho M. Activation of latent murine cytomegalovirus infection: cocultivation, cell transfer, and the effect of immunosuppression. J Infect Dis. 1978 Dec;138(6):890–896. doi: 10.1093/infdis/138.6.890. [DOI] [PubMed] [Google Scholar]
  12. Medearis D. N., Jr Human cytomegalovirus immunization prospects. N Engl J Med. 1977 Jun 2;296(22):1289–1290. doi: 10.1056/NEJM197706022962213. [DOI] [PubMed] [Google Scholar]
  13. Medearis D. N., Jr, Prokay S. L. Effect of immunization of mothers on cytomegalovirus infection in suckling mice. Proc Soc Exp Biol Med. 1978 Apr;157(4):523–527. doi: 10.3181/00379727-157-40089. [DOI] [PubMed] [Google Scholar]
  14. Mims C. A., Gould J. Infection of salivary glands, kidneys, adrenals, ovaries and epithelia by murine cytomegalovirus. J Med Microbiol. 1979 Feb;12(1):113–122. doi: 10.1099/00222615-12-1-113. [DOI] [PubMed] [Google Scholar]
  15. Mäntyjärvi R. A., Selgrade M. J., Collier A. M., Hu S., Pagano J. S. Murine cytomegalovirus infection of epithelial cells in mouse tracheal ring organ culture. J Infect Dis. 1977 Sep;136(3):444–448. doi: 10.1093/infdis/136.3.444. [DOI] [PubMed] [Google Scholar]
  16. Nedrud J. G., Collier A. M., Pagano J. S. Cellular basis for susceptibility to mouse cytomegalovirus: evidence from tracheal organ culture. J Gen Virol. 1979 Dec;45(3):737–744. doi: 10.1099/0022-1317-45-3-737. [DOI] [PubMed] [Google Scholar]
  17. Neff B. J., Weibel R. E., Buynak E. B., McLean A. A., Hilleman M. R. Clinical and laboratory studies of live cytomegalovirus vaccine Ad-169. Proc Soc Exp Biol Med. 1979 Jan;160(1):32–37. doi: 10.3181/00379727-160-40382. [DOI] [PubMed] [Google Scholar]
  18. Osborn J. E., Blazkovec A. A., Walker D. L. Immunosuppression during acute murine cytomegalovirus infection. J Immunol. 1968 Apr;100(4):835–844. [PubMed] [Google Scholar]
  19. Osborn J. E., Walker D. L. Virulence and attenuation of murine cytomegalovirus. Infect Immun. 1971 Feb;3(2):228–236. doi: 10.1128/iai.3.2.228-236.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pagano J. S., Huang E. S. Letter: Vaccination against cytomegalovirus? Lancet. 1974 Feb 23;1(7852):316–317. doi: 10.1016/s0140-6736(74)92629-4. [DOI] [PubMed] [Google Scholar]
  21. Pagano J. S. Infections with cytomegalovirus in bone marrow transplantation: report of a workshop. J Infect Dis. 1975 Jul;132(1):114–120. doi: 10.1093/infdis/132.1.114. [DOI] [PubMed] [Google Scholar]
  22. Plotkin S. A., Farquhar J., Horberger E. Clinical trials of immunization with the Towne 125 strain of human cytomegalovirus. J Infect Dis. 1976 Nov;134(5):470–475. doi: 10.1093/infdis/134.5.470. [DOI] [PubMed] [Google Scholar]
  23. Selgrade M. J., Osborn J. E. Divergence of mouse brain interferon responses following virulent or avirulent Newcastle disease virus inoculation. Proc Soc Exp Biol Med. 1973 May;143(1):12–18. doi: 10.3181/00379727-143-37243. [DOI] [PubMed] [Google Scholar]
  24. Selgrade M. K., Ahmed A., Sell K. W., Gershwin M. E., Steinberg A. D. Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens. J Immunol. 1976 May;116(5):1459–1465. [PubMed] [Google Scholar]
  25. Selgrade M. K., Osborn J. E. Role of macrophages in resistance to murine cytomegalovirus. Infect Immun. 1974 Dec;10(6):1383–1390. doi: 10.1128/iai.10.6.1383-1390.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tinghitella T. J., Booss J. Enhanced immune response late in primary cytomegalovirus infection of mice. J Immunol. 1979 Jun;122(6):2442–2446. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES