Abstract
Inoculation of the replication-defective retrovirus DEF27 (BM5d), packaged as an amphotropic virus pseudotype, into C57BL/6J mice leads to development of murine AIDS. Disease development showed a long incubation period (20 to 24 weeks), was associated with amplification of the BM5d provirus in splenocytes and lymph nodes, and was independent of the presence of exogenous or endogenous replication-competent helper viruses. However, both the onset of disease and amplification of the defective provirus were significantly enhanced by coinfection with the replication-competent B-cell-tropic ecotropic helper virus BM5e. The part of the BM5d viral genome that was essential for the pathogenicity was determined by making precisely engineered alterations in the reading frame of the gag and pol genes of BM5d proviral DNA and examining the ability of the altered amphotropic BM5d pseudotypes to induce the disease in C57BL/6J mice. The results show that expression of the MA (p15) and p12 regions of the gag gene is sufficient for pathogenicity of the BM5d retrovirus.
Full text
PDF










Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Engelhardt J. F., Kellum M. J., Bisat F., Pitha P. M. Retrovirus vector-targeted inducible expression of human beta-interferon gene to B-cells. Virology. 1990 Oct;178(2):419–428. doi: 10.1016/0042-6822(90)90339-s. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Imberti L., Sottini A., Bettinardi A., Puoti M., Primi D. Selective depletion in HIV infection of T cells that bear specific T cell receptor V beta sequences. Science. 1991 Nov 8;254(5033):860–862. doi: 10.1126/science.1948066. [DOI] [PubMed] [Google Scholar]
- Jolicoeur P. Murine acquired immunodeficiency syndrome (MAIDS): an animal model to study the AIDS pathogenesis. FASEB J. 1991 Jul;5(10):2398–2405. doi: 10.1096/fasebj.5.10.2065888. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Herman A., Clements J., Marrack P. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B. J Exp Med. 1992 Feb 1;175(2):387–396. doi: 10.1084/jem.175.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Kubo Y., Nakagawa Y., Kakimi K., Matsui H., Iwashiro M., Kuribayashi K., Masuda T., Hiai H., Hirama T., Yanagawa S. Presence of transplantable T-lymphoid cells in C57BL/6 mice infected with murine AIDS virus. J Virol. 1992 Sep;66(9):5691–5695. doi: 10.1128/jvi.66.9.5691-5695.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laurence J., Hodtsev A. S., Posnett D. N. Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression. Nature. 1992 Jul 16;358(6383):255–259. doi: 10.1038/358255a0. [DOI] [PubMed] [Google Scholar]
- Li Y., Kappes J. C., Conway J. A., Price R. W., Shaw G. M., Hahn B. H. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. J Virol. 1991 Aug;65(8):3973–3985. doi: 10.1128/jvi.65.8.3973-3985.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Overbaugh J., Donahue P. R., Quackenbush S. L., Hoover E. A., Mullins J. I. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. Science. 1988 Feb 19;239(4842):906–910. doi: 10.1126/science.2893454. [DOI] [PubMed] [Google Scholar]
- 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]
- Pozsgay J. M., Reid S., Pitha P. M. Dissociation between lymphoproliferative responses and virus replication in mice with different sensitivities to retrovirus-induced immunodeficiency. J Virol. 1993 Feb;67(2):980–988. doi: 10.1128/jvi.67.2.980-988.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raj N. B., Pitha P. M. Analysis of interferon mRNA in human fibroblast cells induced to produce interferon. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7426–7430. doi: 10.1073/pnas.78.12.7426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swaminathan S., Furey W., Pletcher J., Sax M. Crystal structure of staphylococcal enterotoxin B, a superantigen. Nature. 1992 Oct 29;359(6398):801–806. doi: 10.1038/359801a0. [DOI] [PubMed] [Google Scholar]




