Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1997 Jan;71(1):750–754. doi: 10.1128/jvi.71.1.750-754.1997

Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection.

K Higo 1, Y Kubo 1, Y Iwatani 1, T Ono 1, M Maeda 1, H Hiai 1, T Masuda 1, K Kuribayashi 1, F Zhang 1, T Y Lamin 1, A Adachi 1, A Ishimoto 1
PMCID: PMC191112  PMID: 8985411

Abstract

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/- nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.

Full Text

The Full Text of this article is available as a PDF (235.8 KB).

Selected References

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

  1. Britt W. J., Chesebro B. Use of monoclonal anti-gp70 antibodies to mimic the effects of the Rfv-3 gene in mice with Friend virus-induced leukemia. J Immunol. 1983 May;130(5):2363–2367. [PubMed] [Google Scholar]
  2. Chesebro B., Miyazawa M., Britt W. J. Host genetic control of spontaneous and induced immunity to Friend murine retrovirus infection. Annu Rev Immunol. 1990;8:477–499. doi: 10.1146/annurev.iy.08.040190.002401. [DOI] [PubMed] [Google Scholar]
  3. Chesebro B., Wehrly K., Cloyd M., Britt W., Portis J., Collins J., Nishio J. Characterization of mouse monoclonal antibodies specific for Friend murine leukemia virus-induced erythroleukemia cells: friend-specific and FMR-specific antigens. Virology. 1981 Jul 15;112(1):131–144. doi: 10.1016/0042-6822(81)90619-x. [DOI] [PubMed] [Google Scholar]
  4. Chesebro B., Wehrly K., Doig D., Nishio J. Antibody-induced modulation of Friend virus cell surface antigens decreases virus production by persistent erythroleukemia cells: influence of the Rfv-3 gene. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5784–5788. doi: 10.1073/pnas.76.11.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesebro B., Wehrly K. Identification of a non-H-2 gene (Rfv-3) influencing recovery from viremia and leukemia induced by Friend virus complex. Proc Natl Acad Sci U S A. 1979 Jan;76(1):425–429. doi: 10.1073/pnas.76.1.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Doig D., Chesebro B. Anti-Friend virus antibody is associated with recovery from viremia and loss of viral leukemia cell-surface antigens in leukemic mice. Identification of Rfv-3 as a gene locus influencing antibody production. J Exp Med. 1979 Jul 1;150(1):10–19. doi: 10.1084/jem.150.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ikeda H., Laigret F., Martin M. A., Repaske R. Characterization of a molecularly cloned retroviral sequence associated with Fv-4 resistance. J Virol. 1985 Sep;55(3):768–777. doi: 10.1128/jvi.55.3.768-777.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ikeda H., Odaka T. A cell membrane "gp70" associated with Fv-4 gene: immunological characterization, and tissue and strain distribution. Virology. 1984 Feb;133(1):65–76. doi: 10.1016/0042-6822(84)90426-4. [DOI] [PubMed] [Google Scholar]
  9. Ikeda H., Odaka T. Cellular expression of murine leukemia virus gp70-related antigen on thymocytes of uninfected mice correlates with Fv-4 gene-controlled resistance to Friend leukemia virus infection. Virology. 1983 Jul 15;128(1):127–139. doi: 10.1016/0042-6822(83)90324-0. [DOI] [PubMed] [Google Scholar]
  10. Ikeda H., Sato H., Odaka T. Mapping of the Fv-4 mouse gene controlling resistance to murine leukemia viruses. Int J Cancer. 1981 Aug 15;28(2):237–240. doi: 10.1002/ijc.2910280218. [DOI] [PubMed] [Google Scholar]
  11. Ikeda H., Sugimura H. Fv-4 resistance gene: a truncated endogenous murine leukemia virus with ecotropic interference properties. J Virol. 1989 Dec;63(12):5405–5412. doi: 10.1128/jvi.63.12.5405-5412.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Limjoco T. I., Dickie P., Ikeda H., Silver J. Transgenic Fv-4 mice resistant to Friend virus. J Virol. 1993 Jul;67(7):4163–4168. doi: 10.1128/jvi.67.7.4163-4168.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Limjoco T., Nihrane A., Silver J. Resistance to retroviral infection in transgenic and bone marrow chimeric mice containing Fv4-env-expressing hematopoietic cells. Virology. 1995 Apr 1;208(1):75–83. doi: 10.1006/viro.1995.1131. [DOI] [PubMed] [Google Scholar]
  14. Mackewicz C., Levy J. A. CD8+ cell anti-HIV activity: nonlytic suppression of virus replication. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1039–1050. doi: 10.1089/aid.1992.8.1039. [DOI] [PubMed] [Google Scholar]
  15. Masuda M., Yoshikura H. Construction and characterization of the recombinant Moloney murine leukemia viruses bearing the mouse Fv-4 env gene. J Virol. 1990 Mar;64(3):1033–1043. doi: 10.1128/jvi.64.3.1033-1043.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Odaka T., Ikeda H., Yoshikura H., Moriwaki K., Suzuki S. Fv-4: gene controlling resistance to NB-tropic Friend murine leukemia virus. Distribution in wild mice, introduction into genetic background of BALB/c mice, and mapping of chromosomes. J Natl Cancer Inst. 1981 Nov;67(5):1123–1127. [PubMed] [Google Scholar]
  19. Paxton W. A., Martin S. R., Tse D., O'Brien T. R., Skurnick J., VanDevanter N. L., Padian N., Braun J. F., Kotler D. P., Wolinsky S. M. Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nat Med. 1996 Apr;2(4):412–417. doi: 10.1038/nm0496-412. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Rowland-Jones S., Sutton J., Ariyoshi K., Dong T., Gotch F., McAdam S., Whitby D., Sabally S., Gallimore A., Corrah T. HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nat Med. 1995 Jan;1(1):59–64. doi: 10.1038/nm0195-59. [DOI] [PubMed] [Google Scholar]
  22. Schultz K. R., Klarnet J. P., Gieni R. S., HayGlass K. T., Greenberg P. D. The role of B cells for in vivo T cell responses to a Friend virus-induced leukemia. Science. 1990 Aug 24;249(4971):921–923. doi: 10.1126/science.2118273. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Suzuki S. FV-4: a new gene affecting the splenomegaly induction by Friend leukemia virus. Jpn J Exp Med. 1975 Dec;45(6):473–478. [PubMed] [Google Scholar]
  25. Suzuki S., Matsubara S. Isolation of Friend leukemia virus resistant line from non-inbred mouse colony. Jpn J Exp Med. 1975 Dec;45(6):467–471. [PubMed] [Google Scholar]
  26. Yoshikura H., Naito Y., Moriwaki K. Unstable resistance of G mouse fibroblasts to ecotropic murine leukemia virus infection. J Virol. 1979 Mar;29(3):1078–1086. doi: 10.1128/jvi.29.3.1078-1086.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yoshikura H., Odaka T. Resistance of G mice to murine leukemia virus infection: apparent disparity in in vivo and in vitro resistances. J Natl Cancer Inst. 1978 Aug;61(2):461–463. [PubMed] [Google Scholar]
  28. Yoshikura H., Odaka T. Surface antigen expressed in hematopoietic cells derived from Fv-4r mouse strains. J Natl Cancer Inst. 1982 Jun;68(6):1005–1009. [PubMed] [Google Scholar]

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

RESOURCES