Abstract
Transgenic mice that expressed the superantigen protein encoded in the C3H exogenous mouse mammary tumor virus long terminal repeat deleted their V beta 14+ T cells during the shaping of their immune repertoire and showed no evidence of virus production in their mammary glands after infection by milk-borne C3H exogenous virus. However, they developed mammary gland tumors that had newly integrated copies of C3H exogenous virus, although the latency of tumor formation was much longer than in their nontransgenic littermates that retained their V beta 14+ T cells. After four generations, infectious C3H virus was completely eliminated from the transgenic mouse pedigree. These data support the hypothesis that endogenous mouse mammary tumor proviruses are retained in the genome as protection against exogenous virus infection and subsequent tumorigenesis and show that there may be natural selection against the virus in vivo.
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.
- Acha-Orbea H., Palmer E. Mls--a retrovirus exploits the immune system. Immunol Today. 1991 Oct;12(10):356–361. doi: 10.1016/0167-5699(91)90066-3. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Choi Y., Marrack P., Kappler J. W. Structural analysis of a mouse mammary tumor virus superantigen. J Exp Med. 1992 Mar 1;175(3):847–852. doi: 10.1084/jem.175.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coffin J. M. Superantigens and endogenous retroviruses: a confluence of puzzles. Science. 1992 Jan 24;255(5043):411–413. doi: 10.1126/science.1310360. [DOI] [PubMed] [Google Scholar]
- Cohen J. C., Shank P. R., Morris V. L., Cardiff R., Varmus H. E. Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse. Cell. 1979 Feb;16(2):333–345. doi: 10.1016/0092-8674(79)90010-2. [DOI] [PubMed] [Google Scholar]
- Dyson P. J., Knight A. M., Fairchild S., Simpson E., Tomonari K. Genes encoding ligands for deletion of V beta 11 T cells cosegregate with mammary tumour virus genomes. Nature. 1991 Feb 7;349(6309):531–532. doi: 10.1038/349531a0. [DOI] [PubMed] [Google Scholar]
- Frankel W. N., Rudy C., Coffin J. M., Huber B. T. Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature. 1991 Feb 7;349(6309):526–528. doi: 10.1038/349526a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Gudkov A. V., Kashkin K. N., Zaitsevskaya T. E., Troyanovsky S. M. Histo-blotting: hybridization in situ detection of specific RNAs on tissue sections transferred on nitrocellulose. Int J Cancer. 1989 Dec 15;44(6):1052–1056. doi: 10.1002/ijc.2910440619. [DOI] [PubMed] [Google Scholar]
- 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]
- Ignatowicz L., Kappler J., Marrack P. The effects of chronic infection with a superantigen-producing virus. J Exp Med. 1992 Apr 1;175(4):917–923. doi: 10.1084/jem.175.4.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak C., Peters G., Pauley R., Morris V., Michalides R., Dudley J., Green M., Davisson M., Prakash O., Vaidya A. A standardized nomenclature for endogenous mouse mammary tumor viruses. J Virol. 1987 May;61(5):1651–1654. doi: 10.1128/jvi.61.5.1651-1654.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MURRAY W. S. MA/My strain of the Marsh albino mouse. J Natl Cancer Inst. 1963 Mar;30:605–610. [PubMed] [Google Scholar]
- Nusse R. The int genes in mammary tumorigenesis and in normal development. Trends Genet. 1988 Oct;4(10):291–295. doi: 10.1016/0168-9525(88)90172-2. [DOI] [PubMed] [Google Scholar]
- Pullen A. M., Choi Y., Kushnir E., Kappler J., Marrack P. The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens. J Exp Med. 1992 Jan 1;175(1):41–47. doi: 10.1084/jem.175.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudy C. K., Kraus E., Palmer E., Huber B. T. Mls-1-like superantigen in the MA/MyJ mouse is encoded by a new mammary tumor provirus that is distinct from Mtv-7. J Exp Med. 1992 Jun 1;175(6):1613–1621. doi: 10.1084/jem.175.6.1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shackleford G. M., Varmus H. E. Construction of a clonable, infectious, and tumorigenic mouse mammary tumor virus provirus and a derivative genetic vector. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9655–9659. doi: 10.1073/pnas.85.24.9655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomonari K., Fairchild S., Rosenwasser O. A. Influence of viral superantigens on V beta- and V alpha-specific positive and negative selection. Immunol Rev. 1993 Feb;131:131–168. doi: 10.1111/j.1600-065x.1993.tb01534.x. [DOI] [PubMed] [Google Scholar]
- Van Nie R., Verstraeten A. A., De Moes J. Genetic transmission of mammary tumour virus by GR mice. Int J Cancer. 1977 Mar 15;19(3):383–390. doi: 10.1002/ijc.2910190316. [DOI] [PubMed] [Google Scholar]
- Woodland D. L., Happ M. P., Gollob K. J., Palmer E. An endogenous retrovirus mediating deletion of alpha beta T cells? Nature. 1991 Feb 7;349(6309):529–530. doi: 10.1038/349529a0. [DOI] [PubMed] [Google Scholar]
- Woodland D. L., Lund F. E., Happ M. P., Blackman M. A., Palmer E., Corley R. B. Endogenous superantigen expression is controlled by mouse mammary tumor proviral loci. J Exp Med. 1991 Nov 1;174(5):1255–1258. doi: 10.1084/jem.174.5.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Nie R., Verstraeten A. A. Studies of genetic transmission of mammary tumour virus by C3Hf mice. Int J Cancer. 1975 Dec 15;16(6):922–931. doi: 10.1002/ijc.2910160606. [DOI] [PubMed] [Google Scholar]