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. 1993 Feb;67(2):980–988. doi: 10.1128/jvi.67.2.980-988.1993

Dissociation between lymphoproliferative responses and virus replication in mice with different sensitivities to retrovirus-induced immunodeficiency.

J M Pozsgay 1, S Reid 1, P M Pitha 1
PMCID: PMC237452  PMID: 8380473

Abstract

Murine AIDS (MAIDS) is induced by a replication-defective virus (BM5d). In susceptible mice (C57BL/6J), inoculation with LP-BM5 murine leukemia virus, which consists of the BM5d virus and replication-competent B-tropic ecotropic (BM5e) and milk cell focus-inducing (BM5-MCF) helper viruses results in the polyclonal proliferation of T and B cells, immunodeficiency, and the expansion of B cells containing the BM5d provirus followed by the development of B-cell lymphomas. Several strains of mice that are resistant to LP-BM5-induced murine AIDS have been identified, and major histocompatibility complex genes as well as non-major histocompatibility complex genes were shown to play a role in this resistance. In the present study, we have examined and compared the replication of the BM5d and BM5e viruses after inoculation of LP-BM5 into sensitive (C57BL/6J) and resistant (C57BL/KSJ) mice. Using a specific polymerase chain reaction, we could detect the BM5d and BM5e proviruses as early as 1 week postinfection in the sensitive mice, and the levels of both viruses increased significantly with the progression of the disease. In contrast, in the resistant C57BL/KSJ mice, replication of BM5d and BM5e was restricted and no BM5d and only very low levels of the BM5e provirus could be detected either at early or late times postinoculation with the LP-BM5 virus mixture. Inoculation with LP-BM5 did not lead to the production of antibodies that could recognize the BM5d-encoded Pr60gag in either the sensitive or resistant mice; however, production of antibodies recognizing the env-related proteins of the helper virus was detected in the resistant but not in the sensitive mice at late times postinfection. Interestingly, inoculation with LP-BM5 increased polyclonal stimulation of spleen cells and decreased mitogen stimulation in both strains of mice. This stimulation of splenocytes persisted in the sensitive mice but decreased after a few weeks in the resistant mice. These results show an early block in BM5d and BM5e replication in the resistant C57BL/KSJ mice and indicate that resistance is a consequence of the inhibition of an onset of the BM5d virus infection and its expansion. However, initial responses to virus infection such as proliferation of spleen cells and response to mitogen are similar in both strains of mice and are therefore not necessarily related to the development of the disease.

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Selected References

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

  1. Aziz D. C., Hanna Z., Jolicoeur P. Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature. 1989 Apr 6;338(6215):505–508. doi: 10.1038/338505a0. [DOI] [PubMed] [Google Scholar]
  2. Cerny A., Hügin A. W., Hardy R. R., Hayakawa K., Zinkernagel R. M., Makino M., Morse H. C., 3rd B cells are required for induction of T cell abnormalities in a murine retrovirus-induced immunodeficiency syndrome. J Exp Med. 1990 Jan 1;171(1):315–320. doi: 10.1084/jem.171.1.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cerny A., Hügin A. W., Holmes K. L., Morse H. C., 3rd CD4+ T cells in murine acquired immunodeficiency syndrome: evidence for an intrinsic defect in the proliferative response to soluble antigen. Eur J Immunol. 1990 Jul;20(7):1577–1581. doi: 10.1002/eji.1830200725. [DOI] [PubMed] [Google Scholar]
  4. Chattopadhyay S. K., Lander M. R., Rands E., Lowy D. R. Structure of endogenous murine leukemia virus DNA in mouse genomes. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5774–5778. doi: 10.1073/pnas.77.10.5774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chattopadhyay S. K., Morse H. C., 3rd, Makino M., Ruscetti S. K., Hartley J. W. Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1989 May;86(10):3862–3866. doi: 10.1073/pnas.86.10.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chattopadhyay S. K., Sengupta D. N., Fredrickson T. N., Morse H. C., 3rd, Hartley J. W. Characteristics and contributions of defective, ecotropic, and mink cell focus-inducing viruses involved in a retrovirus-induced immunodeficiency syndrome of mice. J Virol. 1991 Aug;65(8):4232–4241. doi: 10.1128/jvi.65.8.4232-4241.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheung S. C., Chattopadhyay S. K., Hartley J. W., Morse H. C., 3rd, Pitha P. M. Aberrant expression of cytokine genes in peritoneal macrophages from mice infected with LP-BM5 MuLV, a murine model of AIDS. J Immunol. 1991 Jan 1;146(1):121–127. [PubMed] [Google Scholar]
  8. Cheung S. C., Chattopadhyay S. K., Morse H. C., 3rd, Pitha P. M. Expression of defective virus and cytokine genes in murine AIDS. J Virol. 1991 Feb;65(2):823–828. doi: 10.1128/jvi.65.2.823-828.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Erbe J. G., Green K. A., Crassi K. M., Morse H. C., 3rd, Green W. R. Cytolytic T lymphocytes specific for tumors and infected cells from mice with a retrovirus-induced immunodeficiency syndrome. J Virol. 1992 May;66(5):3251–3256. doi: 10.1128/jvi.66.5.3251-3256.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Farzadegan H., Polis M. A., Wolinsky S. M., Rinaldo C. R., Jr, Sninsky J. J., Kwok S., Griffith R. L., Kaslow R. A., Phair J. P., Polk B. F. Loss of human immunodeficiency virus type 1 (HIV-1) antibodies with evidence of viral infection in asymptomatic homosexual men. A report from the Multicenter AIDS Cohort Study. Ann Intern Med. 1988 Jun;108(6):785–790. doi: 10.7326/0003-4819-108-6-785. [DOI] [PubMed] [Google Scholar]
  11. Fitzpatrick E. A., Bryson J. S., Rhoads C., Kaplan A. M., Cohen D. A. T-deficient transmembrane signaling in CD4+ T cells of retroviral-induced immune-deficient mice. J Immunol. 1992 Jun 1;148(11):3377–3384. [PubMed] [Google Scholar]
  12. Gazzinelli R. T., Makino M., Chattopadhyay S. K., Snapper C. M., Sher A., Hügin A. W., Morse H. C., 3rd CD4+ subset regulation in viral infection. Preferential activation of Th2 cells during progression of retrovirus-induced immunodeficiency in mice. J Immunol. 1992 Jan 1;148(1):182–188. [PubMed] [Google Scholar]
  13. Hamelin-Bourassa D., Skamene E., Gervais F. Susceptibility to a mouse acquired immunodeficiency syndrome is influenced by the H-2. Immunogenetics. 1989;30(4):266–272. doi: 10.1007/BF02421330. [DOI] [PubMed] [Google Scholar]
  14. Hartley J. W., Fredrickson T. N., Yetter R. A., Makino M., Morse H. C., 3rd Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains. J Virol. 1989 Mar;63(3):1223–1231. doi: 10.1128/jvi.63.3.1223-1231.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huang M., Jolicoeur P. Characterization of the gag/fusion protein encoded by the defective Duplan retrovirus inducing murine acquired immunodeficiency syndrome. J Virol. 1990 Dec;64(12):5764–5772. doi: 10.1128/jvi.64.12.5764-5772.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huang M., Simard C., Jolicoeur P. Immunodeficiency and clonal growth of target cells induced by helper-free defective retrovirus. Science. 1989 Dec 22;246(4937):1614–1617. doi: 10.1126/science.2480643. [DOI] [PubMed] [Google Scholar]
  17. Huang M., Simard C., Jolicoeur P. Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus. J Virol. 1992 Apr;66(4):2398–2406. doi: 10.1128/jvi.66.4.2398-2406.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Huang M., Simard C., Kay D. G., Jolicoeur P. The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage. J Virol. 1991 Dec;65(12):6562–6571. doi: 10.1128/jvi.65.12.6562-6571.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hügin A. W., Vacchio M. S., Morse H. C., 3rd A virus-encoded "superantigen" in a retrovirus-induced immunodeficiency syndrome of mice. Science. 1991 Apr 19;252(5004):424–427. doi: 10.1126/science.1850169. [DOI] [PubMed] [Google Scholar]
  20. Klinken S. P., Fredrickson T. N., Hartley J. W., Yetter R. A., Morse H. C., 3rd Evolution of B cell lineage lymphomas in mice with a retrovirus-induced immunodeficiency syndrome, MAIDS. J Immunol. 1988 Feb 15;140(4):1123–1131. [PubMed] [Google Scholar]
  21. Klinman D. M., Morse H. C., 3rd Characteristics of B cell proliferation and activation in murine AIDS. J Immunol. 1989 Feb 15;142(4):1144–1149. [PubMed] [Google Scholar]
  22. LATARJET R., DUPLAN J. F. Experiment and discussion on leukaemogenesis by cell-free extracts of radiation-induced leukaemia in mice. Int J Radiat Biol Relat Stud Phys Chem Med. 1962 Aug;5:339–344. doi: 10.1080/09553006214550911. [DOI] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Makino M., Davidson W. F., Fredrickson T. N., Hartley J. W., Morse H. C., 3rd Effects of non-MHC loci on resistance to retrovirus-induced immunodeficiency in mice. Immunogenetics. 1991;33(5-6):345–351. doi: 10.1007/BF00216693. [DOI] [PubMed] [Google Scholar]
  25. Makino M., Morse H. C., 3rd, Fredrickson T. N., Hartley J. W. H-2-associated and background genes influence the development of a murine retrovirus-induced immunodeficiency syndrome. J Immunol. 1990 Jun 1;144(11):4347–4355. [PubMed] [Google Scholar]
  26. Mann D. L., Murray C., Yarchoan R., Blattner W. A., Goedert J. J. HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS. J Acquir Immune Defic Syndr. 1988;1(1):13–17. [PubMed] [Google Scholar]
  27. Morse H. C., 3rd, Yetter R. A., Via C. S., Hardy R. R., Cerny A., Hayakawa K., Hugin A. W., Miller M. W., Holmes K. L., Shearer G. M. Functional and phenotypic alterations in T cell subsets during the course of MAIDS, a murine retrovirus-induced immunodeficiency syndrome. J Immunol. 1989 Aug 1;143(3):844–850. [PubMed] [Google Scholar]
  28. Mosier D. E., Yetter R. A., Morse H. C., 3rd Functional T lymphocytes are required for a murine retrovirus-induced immunodeficiency disease (MAIDS). J Exp Med. 1987 Jun 1;165(6):1737–1742. doi: 10.1084/jem.165.6.1737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mosier D. E., Yetter R. A., Morse H. C., 3rd Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice. J Exp Med. 1985 Apr 1;161(4):766–784. doi: 10.1084/jem.161.4.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Oie H. K., Gazdar A. F., Lalley P. A., Russell E. K., Minna J. D., DeLarco J., Todaro G. J., Francke U. Mouse chromosome 5 codes for ecotropic murine leukaemia virus cell-surface receptor. Nature. 1978 Jul 6;274(5666):60–62. doi: 10.1038/274060a0. [DOI] [PubMed] [Google Scholar]
  31. Pitha P. M., Biegel D., Yetter R. A., Morse H. C., 3rd Abnormal regulation of IFN-alpha, -beta, and -gamma expression in MAIDS, a murine retrovirus-induced immunodeficiency syndrome. J Immunol. 1988 Nov 15;141(10):3611–3616. [PubMed] [Google Scholar]
  32. Ruddle N. H., Conta B. S., Leinwand L., Kozak C., Ruddle F., Besmer P., Baltimore D. Assignment of the receptor for ecotropic murine leukemia virus to mouse chromosome 5. J Exp Med. 1978 Aug 1;148(2):451–465. doi: 10.1084/jem.148.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Steel C. M., Ludlam C. A., Beatson D., Peutherer J. F., Cuthbert R. J., Simmonds P., Morrison H., Jones M. HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease. Lancet. 1988 May 28;1(8596):1185–1188. doi: 10.1016/s0140-6736(88)92009-0. [DOI] [PubMed] [Google Scholar]
  35. Yefenof E., Ela C., Kotler M., Vitetta E. S. Induction of IL-4 secretion by the radiation leukemia virus (RadLV): role in autocrine growth stimulation of RadLV infected pre-leukemic cells. Int J Cancer. 1992 Feb 1;50(3):481–485. doi: 10.1002/ijc.2910500325. [DOI] [PubMed] [Google Scholar]
  36. Yetter R. A., Buller R. M., Lee J. S., Elkins K. L., Mosier D. E., Fredrickson T. N., Morse H. C., 3rd CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS). J Exp Med. 1988 Aug 1;168(2):623–635. doi: 10.1084/jem.168.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]

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