Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1997 Oct;71(10):7295–7299. doi: 10.1128/jvi.71.10.7295-7299.1997

Retrovirus-induced target cell activation in the early phases of infection: the mouse mammary tumor virus model.

C Ardavin 1, F Luthi 1, M Andersson 1, L Scarpellino 1, P Martin 1, H Diggelmann 1, H Acha-Orbea 1
PMCID: PMC192072  PMID: 9311805

Abstract

Mouse mammary tumor virus (MMTV) infects B lymphocytes and expresses a superantigen on the cell surface after integration of its reverse-transcribed genome. Superantigen-dependent B- and T-cell activation becomes detectable 2 to 3 days after infection. We show here that before this event, B cells undergo a polyclonal activation which does not involve massive proliferation. This first phase of B-cell activation is T cell independent. Moreover, during the first phase of activation, when only a small fraction of B cells is infected by MMTV(SW), viral DNA is detected only in activated B cells. Such a B-cell activation is also seen after injection of murine leukemia virus but not after injection of vaccinia virus, despite the very similar kinetics and intensity of the immune response. Since retroviruses require activated target cells to induce efficient infection, these data suggest that the early polyclonal retrovirus-induced target cell activation might play an important role in the establishment of retroviral infections.

Full Text

The Full Text of this article is available as a PDF (170.8 KB).

Selected References

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

  1. Acha-Orbea H., MacDonald H. R. Superantigens of mouse mammary tumor virus. Annu Rev Immunol. 1995;13:459–486. doi: 10.1146/annurev.iy.13.040195.002331. [DOI] [PubMed] [Google Scholar]
  2. Acha-Orbea H., Shakhov A. N., Scarpellino L., Kolb E., Müller V., Vessaz-Shaw A., Fuchs R., Blöchlinger K., Rollini P., Billotte J. Clonal deletion of V beta 14-bearing T cells in mice transgenic for mammary tumour virus. Nature. 1991 Mar 21;350(6315):207–211. doi: 10.1038/350207a0. [DOI] [PubMed] [Google Scholar]
  3. Acha-Orbea H., Zinkernagel R. M., Hengartner H. Cytotoxic T cell clone-specific monoclonal antibodies used to select clonotypic antigen-specific cytotoxic T cells. Eur J Immunol. 1985 Jan;15(1):31–36. doi: 10.1002/eji.1830150107. [DOI] [PubMed] [Google Scholar]
  4. Bachmann M. F., Hengartner H., Zinkernagel R. M. T helper cell-independent neutralizing B cell response against vesicular stomatitis virus: role of antigen patterns in B cell induction? Eur J Immunol. 1995 Dec;25(12):3445–3451. doi: 10.1002/eji.1830251236. [DOI] [PubMed] [Google Scholar]
  5. Bukrinsky M. I., Haggerty S., Dempsey M. P., Sharova N., Adzhubel A., Spitz L., Lewis P., Goldfarb D., Emerman M., Stevenson M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993 Oct 14;365(6447):666–669. doi: 10.1038/365666a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Choi Y., Kappler J. W., Marrack P. A superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus. Nature. 1991 Mar 21;350(6315):203–207. doi: 10.1038/350203a0. [DOI] [PubMed] [Google Scholar]
  7. Del Prete G., De Carli M., D'Elios M. M., Fleckenstein I. M., Fickenscher H., Fleckenstein B., Almerigogna F., Romagnani S. Polyclonal B cell activation induced by herpesvirus saimiri-transformed human CD4+ T cell clones. Role for membrane TNF-alpha/TNF-alpha receptors and CD2/CD58 interactions. J Immunol. 1994 Dec 1;153(11):4872–4879. [PubMed] [Google Scholar]
  8. Gao W. Y., Cara A., Gallo R. C., Lori F. Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8925–8928. doi: 10.1073/pnas.90.19.8925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Golovkina T. V., Chervonsky A., Dudley J. P., Ross S. R. Transgenic mouse mammary tumor virus superantigen expression prevents viral infection. Cell. 1992 May 15;69(4):637–645. doi: 10.1016/0092-8674(92)90227-4. [DOI] [PubMed] [Google Scholar]
  10. Held W., Shakhov A. N., Izui S., Waanders G. A., Scarpellino L., MacDonald H. R., Acha-Orbea H. Superantigen-reactive CD4+ T cells are required to stimulate B cells after infection with mouse mammary tumor virus. J Exp Med. 1993 Feb 1;177(2):359–366. doi: 10.1084/jem.177.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Held W., Shakhov A. N., Waanders G., Scarpellino L., Luethy R., Kraehenbuhl J. P., MacDonald H. R., Acha-Orbea H. An exogenous mouse mammary tumor virus with properties of Mls-1a (Mtv-7). J Exp Med. 1992 Jun 1;175(6):1623–1633. doi: 10.1084/jem.175.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Held W., Waanders G. A., Acha-Orbea H., MacDonald H. R. Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function. J Exp Med. 1994 Dec 1;180(6):2347–2351. doi: 10.1084/jem.180.6.2347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Held W., Waanders G. A., MacDonald H. R., Acha-Orbea H. MHC class II hierarchy of superantigen presentation predicts efficiency of infection with mouse mammary tumor virus. Int Immunol. 1994 Sep;6(9):1403–1407. doi: 10.1093/intimm/6.9.1403. [DOI] [PubMed] [Google Scholar]
  14. Held W., Waanders G. A., Shakhov A. N., Scarpellino L., Acha-Orbea H., MacDonald H. R. Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission. Cell. 1993 Aug 13;74(3):529–540. doi: 10.1016/0092-8674(93)80054-i. [DOI] [PubMed] [Google Scholar]
  15. Krummenacher C., Diggelmann H., Acha-Orbea H. In vivo effects of a recombinant vaccinia virus expressing a mouse mammary tumor virus superantigen. J Virol. 1996 May;70(5):3026–3031. doi: 10.1128/jvi.70.5.3026-3031.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Liao N. S., Maltzman J., Raulet D. H. Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells. J Exp Med. 1989 Jul 1;170(1):135–143. doi: 10.1084/jem.170.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nicoletti I., Migliorati G., Pagliacci M. C., Grignani F., Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 1991 Jun 3;139(2):271–279. doi: 10.1016/0022-1759(91)90198-o. [DOI] [PubMed] [Google Scholar]
  18. Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
  19. Nusse R., Varmus H. E. Wnt genes. Cell. 1992 Jun 26;69(7):1073–1087. doi: 10.1016/0092-8674(92)90630-u. [DOI] [PubMed] [Google Scholar]
  20. Payne J., Huber B. T., Cannon N. A., Schneider R., Schilham M. W., Acha-Orbea H., MacDonald H. R., Hengartner H. Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7695–7698. doi: 10.1073/pnas.85.20.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Price P., Olver S. D., Gibbons A. E., Shellam G. R. B-cell activation following murine cytomegalovirus infection: implications for autoimmunity. Immunology. 1993 Jan;78(1):14–21. [PMC free article] [PubMed] [Google Scholar]
  22. Roe T., Reynolds T. C., Yu G., Brown P. O. Integration of murine leukemia virus DNA depends on mitosis. EMBO J. 1993 May;12(5):2099–2108. doi: 10.1002/j.1460-2075.1993.tb05858.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rott O., Charreire J., Mignon-Godefroy K., Cash E. B cell superstimulatory influenza virus activates peritoneal B cells. J Immunol. 1995 Jul 1;155(1):134–142. [PubMed] [Google Scholar]
  24. Scherer M. T., Ignatowicz L., Winslow G. M., Kappler J. W., Marrack P. Superantigens: bacterial and viral proteins that manipulate the immune system. Annu Rev Cell Biol. 1993;9:101–128. doi: 10.1146/annurev.cb.09.110193.000533. [DOI] [PubMed] [Google Scholar]
  25. Testi R., D'Ambrosio D., De Maria R., Santoni A. The CD69 receptor: a multipurpose cell-surface trigger for hematopoietic cells. Immunol Today. 1994 Oct;15(10):479–483. doi: 10.1016/0167-5699(94)90193-7. [DOI] [PubMed] [Google Scholar]
  26. Thorley-Lawson D. A., Nadler L. M., Bhan A. K., Schooley R. T. BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus. J Immunol. 1985 May;134(5):3007–3012. [PubMed] [Google Scholar]
  27. Woodland D. L., Blackman M. A. How do T-cell receptors, MHC molecules and superantigens get together? Immunol Today. 1993 May;14(5):208–212. doi: 10.1016/0167-5699(93)90164-G. [DOI] [PubMed] [Google Scholar]
  28. Yokoyama W. M., Koning F., Kehn P. J., Pereira G. M., Stingl G., Coligan J. E., Shevach E. M. Characterization of a cell surface-expressed disulfide-linked dimer involved in murine T cell activation. J Immunol. 1988 Jul 15;141(2):369–376. [PubMed] [Google Scholar]

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

RESOURCES