Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1996 Sep;70(9):6405–6409. doi: 10.1128/jvi.70.9.6405-6409.1996

Possible origin of murine AIDS (MAIDS) virus: conversion of an endogenous retroviral p12gag sequence to a MAIDS-inducing sequence by frameshift mutations.

Y Kubo 1, K Kakimi 1, K Higo 1, H Kobayashi 1, T Ono 1, Y Iwama 1, K Kuribayashi 1, H Hiai 1, A Adachi 1, A Ishimoto 1
PMCID: PMC190669  PMID: 8709271

Abstract

The murine AIDS (MAIDS) virus has a unique sequence in its p12gag region, which is responsible for MAIDS development. A transcript hybridizing with this sequence is expressed in normal C57BL/6 mice. The transcript, designated Edv, has been previously cloned and sequenced (Y. Kubo, Y. Nakagawa, K. Kakimi, H. Matsui, K. Higo, L. Wang, H. Kobayashi, T. Hirama, and A. Ishimoto, J. Gen. Virol. 75:881-888, 1994). Compared with the nucleotide sequence of the helper LP-BM5 ecotropic virus, the pathogenic replication-defective MAIDS virus has a 16-bp deletion and a 1-bp insertion in the 5' and 3' regions of the p12gag sequence, respectively, and the Edv transcript contains only a 3-bp deletion. Therefore, the amino acid sequence of the defective MAIDS virus p12gag region is not homologous to that of the helper virus and the Edv transcript because of the frameshift. To determine whether the amino acid sequence resulting from the frameshift is critical for MAIDS development, we constructed chimeric viruses that contained the p12gag regions of the helper virus and the Edv transcript, respectively, with and without the same frame as the defective MAIDS virus by the artificial frameshift mutations. The mutant viruses with the frameshift mutations induced MAIDS in inoculated mice, but the viruses without the mutations did not. These results suggested that the MAIDS virus was generated by frameshift mutations in the p12gag region of Edv or a related sequence.

Full Text

The Full Text of this article is available as a PDF (400.8 KB).

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. Buller R. M., Yetter R. A., Fredrickson T. N., Morse H. C., 3rd Abrogation of resistance to severe mousepox in C57BL/6 mice infected with LP-BM5 murine leukemia viruses. J Virol. 1987 Feb;61(2):383–387. doi: 10.1128/jvi.61.2.383-387.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casabianca A., Magnani M. A p12 gag gene homologue is present in the mouse genome. Biochem Mol Biol Int. 1994 Mar;32(4):691–696. [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. Cho B. C., Shaughnessy J. D., Jr, Largaespada D. A., Bedigian H. G., Buchberg A. M., Jenkins N. A., Copeland N. G. Frequent disruption of the Nf1 gene by a novel murine AIDS virus-related provirus in BXH-2 murine myeloid lymphomas. J Virol. 1995 Nov;69(11):7138–7146. doi: 10.1128/jvi.69.11.7138-7146.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coffin J. M. Genetic diversity and evolution of retroviruses. Curr Top Microbiol Immunol. 1992;176:143–164. doi: 10.1007/978-3-642-77011-1_10. [DOI] [PubMed] [Google Scholar]
  9. Deng W. P., Nickoloff J. A. Site-directed mutagenesis of virtually any plasmid by eliminating a unique site. Anal Biochem. 1992 Jan;200(1):81–88. doi: 10.1016/0003-2697(92)90280-k. [DOI] [PubMed] [Google Scholar]
  10. Gayama S., Vaupel B. A., Kanagawa O. Sequence heterogeneity of murine acquired immunodeficiency syndrome virus: the role of endogenous virus. Int Immunol. 1995 May;7(5):861–868. doi: 10.1093/intimm/7.5.861. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Kanagawa O., Vaupel B. A., Korsmeyer S. J., Russell J. H. Apoptotic death of lymphocytes in murine acquired immunodeficiency syndrome: involvement of Fas-Fas ligand interaction. Eur J Immunol. 1995 Sep;25(9):2421–2427. doi: 10.1002/eji.1830250902. [DOI] [PubMed] [Google Scholar]
  14. Kubo Y., Kakimi K., Higo K., Wang L., Kobayashi H., Kuribayashi K., Masuda T., Hirama T., Ishimoto A. The p15gag and p12gag regions are both necessary for the pathogenicity of the murine AIDS virus. J Virol. 1994 Sep;68(9):5532–5537. doi: 10.1128/jvi.68.9.5532-5537.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kubo Y., Nakagawa Y., Kakimi K., Matsui H., Higo K., Wang L., Kobayashi H., Hirama T., Ishimoto A. Molecular cloning and characterization of a murine AIDS virus-related endogenous transcript expressed in C57BL/6 mice. J Gen Virol. 1994 Apr;75(Pt 4):881–888. doi: 10.1099/0022-1317-75-4-881. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Markowitz D., Goff S., Bank A. Construction and use of a safe and efficient amphotropic packaging cell line. Virology. 1988 Dec;167(2):400–406. [PubMed] [Google Scholar]
  20. Morse H. C., 3rd, Chattopadhyay S. K., Makino M., Fredrickson T. N., Hügin A. W., Hartley J. W. Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS. AIDS. 1992 Jul;6(7):607–621. doi: 10.1097/00002030-199207000-00001. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Nakagawa Y., Kakimi K., Ling W., Kubo Y., Higo K., Masuda T., Kuribayashi K., Iwashiro M., Komatz Y., Hirama T. Inhibition of murine AIDS (MAIDS), development by the transplantation of bone marrow cells carrying the Fv-4 resistance gene to MAIDS virus-infected mice. J Virol. 1994 Mar;68(3):1438–1441. doi: 10.1128/jvi.68.3.1438-1441.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Portnoi D., Stall A. M., Schwartz D., Merigan T. C., Herzenberg L. A., Basham T. Zidovudine (azido dideoxythymidine) inhibits characteristic early alterations of lymphoid cell populations in retrovirus-induced murine AIDS. J Immunol. 1990 Mar 1;144(5):1705–1710. [PubMed] [Google Scholar]
  24. Pozsgay J. M., Beilharz M. W., Wines B. D., Hess A. D., Pitha P. M. The MA (p15) and p12 regions of the gag gene are sufficient for the pathogenicity of the murine AIDS virus. J Virol. 1993 Oct;67(10):5989–5999. doi: 10.1128/jvi.67.10.5989-5999.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES