Summary
Among murine leukemia viruses (MuLV) present in the LP-BM5 virus mixture, the agent etiologic for an acquired immunodeficiency syndrome (MAIDS) is replication defective, containing only a single open reading frame which includes all ofgag. The Gag polyprotein encoded by the defective virus, termed BM5def, differs most in p12 from that of nonpathogenic ecotropic virus (BM5eco). As one approach to examining the role of p12 in disease, the ecotropic and defective virus forms of the protein, synthesized in bacteria, were used to immunize three strains of mice differing in their sensitivity to MAIDS. In each strain, both proteins elicited substantial antibody responses that were cross-reactive with either p12 and recognized the proteins as part of intact viral Gag polyproteins. Immunization with either p12 before infection with LP-BM5 viruses had no effect on the sensitivity or resistance of mice to MAIDS or on the extent of helper virus spread. The variant p12 of BM5def, when presented on its own, is thus not a crucial antigenic determinant of disease. Alternative mechanisms by which BM5def may contribute to MAIDS are discussed.
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References
Aziz DC, Hanna Z, Jolicoeur P (1989) Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature 338: 505–508
Buller RML, Yetter RA, Fredrickson TN, Morse HC III (1987) Abrogation of resistance to severe mousepox in C 57 BL/6 mice infected with LP-BM 5 murine leukemia viruses. J Virol 61: 383–387
Chattopadhyay SK, Morse HC III, Makino M, Ruscetti SK, Hartley JW (1989) Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci USA 86: 3862–3866
Chattopadhyay SK, SenGupta DN, Fredrickson TN, Morse HC III, Hartley JW (1991) Characteristics and contributions of defective, ecotropic and MCF viruses involved in a retrovirus-induced immunodeficiency syndrome of mice. J Virol 65: 4232–4241
Chesebro B, Britt W, Evans L, Wehrly K, Nishio J, Cloyd M (1983) Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of Friend MCF and Friend ecotropic murine leukemia virus. Virology 127: 134–148
Cloyd MW, Hartley JW, Rowe WP (1980) Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. J Exp Med 151: 542–552
Dickson C, Eisenman R, Fan H, Hunter E, Teich N (1982) Protein biosynthesis and assembly. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 513–648
Hartley JW, Fredrickson TN, Yetter RA, Makino M, Morse HC III (1989) Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains. J Virol 63: 1223–1231
Hartley JW, Rowe WP (1975) Clonal cell lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology 65: 128–134
Hartley JW, Wolford NK, Old LJ, Rowe WP (1977) A new class of murine leukemia viruses associated with development of spontaneous lymphomas. Proc Natl Acad Sci USA 74: 789–792
Huang M, Jolicoeur P (1990) Characterization of the gag/fusion protein encoded by the defective Duplan retrovirus inducing murine acquired immunodeficiency syndrome. J Virol 64: 5764–5772
Huang M, Simard C, Jolicoeur P (1989) Immunodeficiency and clonal growth of target cells induced by helper-free defective retrovirus. Science 246: 1614–1617
Huang M, Simard C, Jolicoeur P (1992) Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus. J Virol 66: 2398–2406
Hügin AW, Vacchio MS, Morse HC III (1991) A virus-encoded “superantigen” in a retrovirus-induced immunodeficiency syndrome of mice. Science 252: 424–427
Klinken SP, Fredrickson TN, Hartley JW, Yetter RA, Morse HC III (1988) Evolution of B cell lineage lymphomas in mice with a retrovirus-induced immunodeficiency syndrome, MAIDS. J Immunol 140: 1123–1131
Klinman DM, Morse HC III (1989) Characteristics of B cell proliferation and activation in murine AIDS. J Immunol 142: 1144–1149
Makino M, Morse HC III, Fredrickson TN, Hartley JW (1990) H-2-associated and background genes influence the development of a murine retrovirus-induced immunodeficiency syndrome. J Immunol 144: 4347–4355
Makino M, Chattopadhyay SK, Hartley JW, Morse HC III (1992) Analysis of role of CD 8+ T cells in resistance to murine AIDS in A/J mice. J Immunol 149: 1702–1706
McGrath M, Witte O, Pincus T, Weissman IL (1978) Retrovirus purification: method that conserves envelope glycoprotein and maximizes infectivity. J Virol 25: 923–927
Morse HC III, Yetter RA, Via CS, Hardy RR, Cerny A, Hayakawa K, Hügin AW, Miller MW, Holmes KL, Shearer GM. (1989) Functional and phenotypic alterations in T cell subsets during the course of MAIDS, a murine retrovirus-induced immunodeficiency syndrome. J Immunol 143: 844–850
Mosier DE, Yetter RA, Morse HC III (1985) Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C 57 BL/6 mice. J Exp Med 161: 766–784
Rowe WP, Pugh WE, Hartley JW (1970) Plaque assay techniques for murine leukemia viruses. Virology 42: 1136–1139
Smith DB, Johnson KS (1988) Single-step purification of polypeptides expressed inEscherichia coli as fusions with glutathione S-transferase. Gene 67: 31–40
Yetter RA, Buller RML, Lee JS, Elkins KL, Mosier DE, Fredrickson TN, Morse HC III (1988) CD 4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS). J Exp Med 168: 623–635
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Tang, Y., Hügin, A.W., Hartley, J.W. et al. Effects of immunization with the p12 proteins of LP-BM5 defective and ecotropic viruses on development of MAIDS. Archives of Virology 129, 155–166 (1993). https://doi.org/10.1007/BF01316892
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DOI: https://doi.org/10.1007/BF01316892