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. 1995 Nov;69(11):6847–6851. doi: 10.1128/jvi.69.11.6847-6851.1995

Immunogenic determinants of a neuropathogenic murine leukemia virus.

D S Robbins 1, M P Remington 1, M Sarzotti 1, D St Louis 1, P M Hoffman 1
PMCID: PMC189598  PMID: 7474098

Abstract

Previous studies of Cas-Br-M murine leukemia virus (MuLV) (Cas-MuLV) infection demonstrated that cytotoxic T cells (CTL) of the CD8+ phenotype play a role in resistance to the neuropathogenic effects of the virus in NFS/N mice. In the current study, we sought to identify the Cas-MuLV epitopes that are immunogenic for the CTL response. Infection of adult NFS/N mice with a well-characterized neuropathogenic variant of Friend MuLV, PVC-211 MuLV (PVC-MuLV), was not immunogenic for MuLV-specific CTL. Therefore, we constructed chimeric viruses between Cas-MuLV and PVC-MuLV. Infectious chimeras contained the Cas-MuLV env gene on a PVC-MuLV background (PVC-CasenvMuLV) and the PVC-MuLV env gene on a Cas-MuLV background (Cas-PVCenvMuLV). Cas-MuLV-specific CTL were found following inoculation of both the chimeric viruses and the parental Cas-MuLV but not the parental PVC-MuLV, despite evidence of antibody responses to both parental and chimeric MuLV. CTL generated in response to infection with PVC-CasenvMuLV and Cas-PVCenvMuLV were exclusively of the CD8+ phenotype. These results indicate that both the env and gag-pol regions of Cas-MuLV express epitopes that are immunogenic for CTL.

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Selected References

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  1. Borrow P., Lewicki H., Hahn B. H., Shaw G. M., Oldstone M. B. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol. 1994 Sep;68(9):6103–6110. doi: 10.1128/jvi.68.9.6103-6110.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DesGroseillers L., Barrette M., Jolicoeur P. Physical mapping of the paralysis-inducing determinant of a wild mouse ecotropic neurotropic retrovirus. J Virol. 1984 Nov;52(2):356–363. doi: 10.1128/jvi.52.2.356-363.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goff S., Traktman P., Baltimore D. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J Virol. 1981 Apr;38(1):239–248. doi: 10.1128/jvi.38.1.239-248.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  5. Hoffman P. M., Cimino E. F., Robbins D. S., Broadwell R. D., Powers J. M., Ruscetti S. K. Cellular tropism and localization in the rodent nervous system of a neuropathogenic variant of Friend murine leukemia virus. Lab Invest. 1992 Sep;67(3):314–321. [PubMed] [Google Scholar]
  6. Hoffman P. M., Cimino E. F., Robbins D. S. Effects of viral specific cytotoxic lymphocytes on the expression of murine leukemia virus induced neurologic disease. J Neuroimmunol. 1991 Aug;33(2):157–165. doi: 10.1016/0165-5728(91)90059-g. [DOI] [PubMed] [Google Scholar]
  7. Hoffman P. M., Robbins D. S., Morse H. C., 3rd Role of immunity in age-related resistance to paralysis after murine leukemia virus infection. J Virol. 1984 Dec;52(3):734–738. doi: 10.1128/jvi.52.3.734-738.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holt C. A., Osorio K., Lilly F. Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities. J Exp Med. 1986 Jul 1;164(1):211–226. doi: 10.1084/jem.164.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hom R. C., Finberg R. W., Mullaney S., Ruprecht R. M. Protective cellular retroviral immunity requires both CD4+ and CD8+ immune T cells. J Virol. 1991 Jan;65(1):220–224. doi: 10.1128/jvi.65.1.220-224.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ishihara C., Miyazawa M., Nishio J., Chesebro B. Induction of protective immunity to Friend murine leukemia virus in genetic nonresponders to virus envelope protein. J Immunol. 1991 Jun 1;146(11):3958–3963. [PubMed] [Google Scholar]
  11. Jolicoeur P., Nicolaiew N., DesGroseillers L., Rassart E. Molecular cloning of infectious viral DNA from ecotropic neurotropic wild mouse retrovirus. J Virol. 1983 Mar;45(3):1159–1163. doi: 10.1128/jvi.45.3.1159-1163.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Klarnet J. P., Kern D. E., Okuno K., Holt C., Lilly F., Greenberg P. D. FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens. J Exp Med. 1989 Feb 1;169(2):457–467. doi: 10.1084/jem.169.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Masuda M., Remington M. P., Hoffman P. M., Ruscetti S. K. Molecular characterization of a neuropathogenic and nonerythroleukemogenic variant of Friend murine leukemia virus PVC-211. J Virol. 1992 May;66(5):2798–2806. doi: 10.1128/jvi.66.5.2798-2806.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matis L. A., Ruscetti S. K., Longo D. L., Jacobson S., Brown E. J., Zinn S., Kruisbeek A. M. Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen. J Immunol. 1985 Jul;135(1):703–713. [PubMed] [Google Scholar]
  15. Miyazawa M., Nishio J., Chesebro B. Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene. J Virol. 1992 Jul;66(7):4497–4507. doi: 10.1128/jvi.66.7.4497-4507.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mushinski J. F., Davidson W. F., Morse H. C., 3rd Activation of cellular oncogenes in human and mouse leukemia-lymphomas: spontaneous and induced oncogene expression in murine B lymphocytic neoplasms. Cancer Invest. 1987;5(4):345–368. [PubMed] [Google Scholar]
  17. Paquette Y., Hanna Z., Savard P., Brousseau R., Robitaille Y., Jolicoeur P. Retrovirus-induced murine motor neuron disease: mapping the determinant of spongiform degeneration within the envelope gene. Proc Natl Acad Sci U S A. 1989 May;86(10):3896–3900. doi: 10.1073/pnas.86.10.3896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Perryman S. M., McAtee F. J., Portis J. L. Complete nucleotide sequence of the neurotropic murine retrovirus CAS-BR-E. Nucleic Acids Res. 1991 Apr 11;19(7):1707–1707. doi: 10.1093/nar/19.7.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Plata F., Langlade-Demoyen P., Abastado J. P., Berbar T., Kourilsky P. Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Cell. 1987 Jan 30;48(2):231–240. doi: 10.1016/0092-8674(87)90426-0. [DOI] [PubMed] [Google Scholar]
  20. Portis J. L., Czub S., Garon C. F., McAtee F. J. Neurodegenerative disease induced by the wild mouse ecotropic retrovirus is markedly accelerated by long terminal repeat and gag-pol sequences from nondefective Friend murine leukemia virus. J Virol. 1990 Apr;64(4):1648–1656. doi: 10.1128/jvi.64.4.1648-1656.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Remington M. P., Hoffman P. M., Ruscetti S. K., Masuda M. Complete nucleotide sequence of a neuropathogenic variant of Friend murine leukemia virus PVC-211. Nucleic Acids Res. 1992 Jun 25;20(12):3249–3249. doi: 10.1093/nar/20.12.3249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Robbins D. S., Hoffman P. M. Virus-specific cytotoxic lymphocyte response in a neurotropic murine leukemia virus infection. J Neuroimmunol. 1991 Jan;31(1):9–17. doi: 10.1016/0165-5728(91)90081-h. [DOI] [PubMed] [Google Scholar]
  23. Robertson M. N., Spangrude G. J., Hasenkrug K., Perry L., Nishio J., Wehrly K., Chesebro B. Role and specificity of T-cell subsets in spontaneous recovery from Friend virus-induced leukemia in mice. J Virol. 1992 Jun;66(6):3271–3277. doi: 10.1128/jvi.66.6.3271-3277.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  25. Saha K., Wong P. K. Protective role of cytotoxic lymphocytes against murine leukemia virus-induced neurologic disease and immunodeficiency is enhanced by the presence of helper T cells. Virology. 1992 Jun;188(2):921–925. doi: 10.1016/0042-6822(92)90554-3. [DOI] [PubMed] [Google Scholar]
  26. Szurek P. F., Yuen P. H., Jerzy R., Wong P. K. Identification of point mutations in the envelope gene of Moloney murine leukemia virus TB temperature-sensitive paralytogenic mutant ts1: molecular determinants for neurovirulence. J Virol. 1988 Jan;62(1):357–360. doi: 10.1128/jvi.62.1.357-360.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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