Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses.
Abstract
Two novel exogenous mouse mammary tumor viruses (MMTV), BALB2 and BALB14, that encode superantigens (Sags) with Vbeta2+ and Vbeta14+ specificities, respectively, were found in the BALB/cT mouse strain. BALB/cT females were crossed with AKR/J males to generate F1 females. Foster nursing of BALB/cT mice on (BALB/cT x AKR/J)F1 mothers resulted in the generation of a new mouse strain, BALB/cLA, that had acquired a new exogenous MMTV (hereafter called LA) with a Vbeta6+/Vbeta8.1+-T-cell-specific Sag. Sequence analysis of the long terminal repeats of the BALB2, BALB14, and LA viruses indicated that LA virus resulted from recombination between BALB14 and the endogenous Mtv-7 provirus. Mtv-7 is expressed only in lymphoid tissues but not the mammary glands of Mtv-7-containing mouse strains such as AKR. In contrast, LA virus was highly expressed in the mammary gland, although it had the sag-specific region from Mtv-7. The LA virus, as well as different recombinant viruses expressed in the mammary glands of (BALB/cT x AKR/J)F1 mice, acquired a specific DNA sequence from BALB14 virus that is required for the mammary-gland-specific expression of MMTV. Since the Sag encoded by LA virus strongly stimulated cognate T cells in vivo, selection for recombinant virus with the Mtv-7 sag most likely occurred because the increased T-cell proliferation resulted in greater lymphoid and mammary gland cell infection. As a result of the higher virus titer, 80% of BALB/cLA females developed mammary gland tumors, although the incidence was only 40% in BALB/cT mice.
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- Acha-Orbea H, Shakhov AN, Scarpellino L, Kolb E, Müller V, Vessaz-Shaw A, Fuchs R, Blöchlinger K, Rollini P, Billotte J, et al. Clonal deletion of V beta 14-bearing T cells in mice transgenic for mammary tumour virus. Nature. 1991 Mar 21;350(6315):207–211. [PubMed] [Google Scholar]
- Ando Y, Wajjwalku W, Niimi N, Hiromatsu K, Morishima T, Yoshikai Y. Concomitant infection with exogenous mouse mammary tumor virus encoding I-E-dependent superantigen in I-E-negative mouse strain. J Immunol. 1995 Jun 15;154(12):6219–6226. [PubMed] [Google Scholar]
- Beutner U, Frankel WN, Cote MS, Coffin JM, Huber BT. Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5432–5436. [PMC free article] [PubMed] [Google Scholar]
- Brandt-Carlson C, Butel JS, Wheeler D. Phylogenetic and structural analyses of MMTV LTR ORF sequences of exogenous and endogenous origins. Virology. 1993 Mar;193(1):171–185. [PubMed] [Google Scholar]
- Burdon TG, Maitland KA, Clark AJ, Wallace R, Watson CJ. Regulation of the sheep beta-lactoglobulin gene by lactogenic hormones is mediated by a transcription factor that binds an interferon-gamma activation site-related element. Mol Endocrinol. 1994 Nov;8(11):1528–1536. [PubMed] [Google Scholar]
- Ivashkiv LB. Cytokines and STATs: how can signals achieve specificity? Immunity. 1995 Jul;3(1):1–4. [PubMed] [Google Scholar]
- Choi Y, Kappler JW, 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. [PubMed] [Google Scholar]
- Choi YW, Henrard D, Lee I, Ross SR. The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice. J Virol. 1987 Oct;61(10):3013–3019. [PMC free article] [PubMed] [Google Scholar]
- Drohan W, Teramoto YA, Medina D, Schlom J. Isolation and characterization of a new mouse mammary tumor virus from BALB/c mice. Virology. 1981 Oct 15;114(1):175–186. [PubMed] [Google Scholar]
- Frankel WN, Rudy C, Coffin JM, Huber BT. Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature. 1991 Feb 7;349(6309):526–528. [PubMed] [Google Scholar]
- Fritsch EF, Temin HM. Inhibition of viral DNA synthesis in stationary chicken embryo fibroblasts infected with avian retroviruses. J Virol. 1977 Nov;24(2):461–469. [PMC free article] [PubMed] [Google Scholar]
- Golovkina TV, Dudley JP, Jaffe AB, Ross SR. Mouse mammary tumor viruses with functional superantigen genes are selected during in vivo infection. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4828–4832. [PMC free article] [PubMed] [Google Scholar]
- Golovkina TV, Chervonsky A, Dudley JP, Ross SR. Transgenic mouse mammary tumor virus superantigen expression prevents viral infection. Cell. 1992 May 15;69(4):637–645. [PubMed] [Google Scholar]
- Golovkina TV, Chervonsky A, Prescott JA, Janeway CA, Jr, Ross SR. The mouse mammary tumor virus envelope gene product is required for superantigen presentation to T cells. J Exp Med. 1994 Feb 1;179(2):439–446. [PMC free article] [PubMed] [Google Scholar]
- Golovkina TV, Jaffe AB, Ross SR. Coexpression of exogenous and endogenous mouse mammary tumor virus RNA in vivo results in viral recombination and broadens the virus host range. J Virol. 1994 Aug;68(8):5019–5026. [PMC free article] [PubMed] [Google Scholar]
- Golovkina TV, Prakash O, Ross SR. Endogenous mouse mammary tumor virus Mtv-17 is involved in Mtv-2-induced tumorigenesis in GR mice. Virology. 1996 Apr 1;218(1):14–22. [PubMed] [Google Scholar]
- Guyer NB, Severns CW, Wong P, Feghali CA, Wright TM. IFN-gamma induces a p91/Stat1 alpha-related transcription factor with distinct activation and binding properties. J Immunol. 1995 Oct 1;155(7):3472–3480. [PubMed] [Google Scholar]
- Held W, Shakhov AN, Waanders G, Scarpellino L, Luethy R, Kraehenbuhl JP, MacDonald HR, 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. [PMC free article] [PubMed] [Google Scholar]
- Held W, Shakhov AN, Izui S, Waanders GA, Scarpellino L, MacDonald HR, 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. [PMC free article] [PubMed] [Google Scholar]
- Held W, Waanders GA, Shakhov AN, Scarpellino L, Acha-Orbea H, MacDonald HR. Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission. Cell. 1993 Aug 13;74(3):529–540. [PubMed] [Google Scholar]
- Henrard D, Ross SR. Endogenous mouse mammary tumor virus is expressed in several organs in addition to the lactating mammary gland. J Virol. 1988 Aug;62(8):3046–3049. [PMC free article] [PubMed] [Google Scholar]
- Hodes RJ, Novick MB, Palmer LD, Knepper JE. Association of a V beta 2-specific superantigen with a tumorigenic milk-borne mouse mammary tumor virus. J Immunol. 1993 Feb 15;150(4):1422–1428. [PubMed] [Google Scholar]
- Ihle JN, Kerr IM. Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet. 1995 Feb;11(2):69–74. [PubMed] [Google Scholar]
- Jouvin-Marche E, Marche PN, Six A, Liebe-Gris C, Voegtle D, Cazenave PA. Identification of an endogenous mammary tumor virus involved in the clonal deletion of V beta 2 T cells. Eur J Immunol. 1993 Nov;23(11):2758–2764. [PubMed] [Google Scholar]
- Kang JJ, Schwegel T, Knepper JE. Sequence similarity between the long terminal repeat coding regions of mammary-tumorigenic BALB/cV and renal-tumorigenic C3H-K strains of mouse mammary tumor virus. Virology. 1993 Sep;196(1):303–308. [PubMed] [Google Scholar]
- Kozak C, Peters G, Pauley R, Morris V, Michalides R, Dudley J, Green M, Davisson M, Prakash O, Vaidya A, et al. A standardized nomenclature for endogenous mouse mammary tumor viruses. J Virol. 1987 May;61(5):1651–1654. [PMC free article] [PubMed] [Google Scholar]
- Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. [PubMed] [Google Scholar]
- Marrack P, Kushnir E, Kappler J. A maternally inherited superantigen encoded by a mammary tumour virus. Nature. 1991 Feb 7;349(6309):524–526. [PubMed] [Google Scholar]
- Mohan N, Mottershead D, Subramanyam M, Beutner U, Huber BT. Production and characterization of an Mls-1-specific monoclonal antibody. J Exp Med. 1993 Feb 1;177(2):351–358. [PMC free article] [PubMed] [Google Scholar]
- Mok E, Golovkina TV, Ross SR. A mouse mammary tumor virus mammary gland enhancer confers tissue-specific but not lactation-dependent expression in transgenic mice. J Virol. 1992 Dec;66(12):7529–7532. [PMC free article] [PubMed] [Google Scholar]
- Moore DH, Long CA, Vaidya AB, Sheffield JB, Dion AS, Lasfargues EY. Mammary tumor viruses. Adv Cancer Res. 1979;29:347–418. [PubMed] [Google Scholar]
- Nepomnaschy I, Déroche A, Torello S, Goldman A, Buggiano V, Pasqualini CD, Piazzon I. Popliteal lymph node enlargement induced in syngeneic hosts by T cells from foster-nursed mice. Cell Immunol. 1990 Jun;128(1):175–184. [PubMed] [Google Scholar]
- Niimi N, Wajjwalku W, Ando Y, Nakamura N, Ueda M, Yoshikai Y. A novel V beta 2-specific endogenous mouse mammary tumor virus which is capable of producing a milk-borne exogenous virus. J Virol. 1995 Nov;69(11):7269–7273. [PMC free article] [PubMed] [Google Scholar]
- Pandey R, Ghosh AK, Kumar DV, Bachman BA, Shibata D, Roy-Burman P. Recombination between feline leukemia virus subgroup B or C and endogenous env elements alters the in vitro biological activities of the viruses. J Virol. 1991 Dec;65(12):6495–6508. [PMC free article] [PubMed] [Google Scholar]
- Piazzon I, Goldman A, Torello S, Nepomnaschy I, Deroche A, Dran G. Transmission of an Mls-1a-like superantigen to BALB/c mice by foster-nursing on F1 Mls-1bxa mothers. Sex-influenced onset of clonal deletion. J Immunol. 1994 Aug 15;153(4):1553–1562. [PubMed] [Google Scholar]
- Pullen AM, 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. [PMC free article] [PubMed] [Google Scholar]
- Rammensee HG, Kroschewski R, Frangoulis B. Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells. Nature. 1989 Jun 15;339(6225):541–544. [PubMed] [Google Scholar]
- Ross SR, Hsu CL, Choi Y, Mok E, Dudley JP. Negative regulation in correct tissue-specific expression of mouse mammary tumor virus in transgenic mice. Mol Cell Biol. 1990 Nov;10(11):5822–5829. [PMC free article] [PubMed] [Google Scholar]
- Schaefer TS, Sanders LK, Nathans D. Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9097–9101. [PMC free article] [PubMed] [Google Scholar]
- Schindler C, Darnell JE., Jr Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem. 1995;64:621–651. [PubMed] [Google Scholar]
- Shakhov AN, Wang H, Acha-Orbea H, Pauley RJ, Wei WZ. A new infectious mammary tumor virus in the milk of mice implanted with C4 hyperplastic alveolar nodules. Eur J Immunol. 1993 Nov;23(11):2765–2769. [PubMed] [Google Scholar]
- Stoye JP, Moroni C, Coffin JM. Virological events leading to spontaneous AKR thymomas. J Virol. 1991 Mar;65(3):1273–1285. [PMC free article] [PubMed] [Google Scholar]
- Varmus HE, Padgett T, Heasley S, Simon G, Bishop JM. Cellular functions are required for the synthesis and integration of avian sarcoma virus-specific DNA. Cell. 1977 Jun;11(2):307–319. [PubMed] [Google Scholar]
- Wakao H, Gouilleux F, Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 1994 May 1;13(9):2182–2191. [PMC free article] [PubMed] [Google Scholar]
- Wellinger RJ, Garcia M, Vessaz A, Diggelmann H. Exogenous mouse mammary tumor virus proviral DNA isolated from a kidney adenocarcinoma cell line contains alterations in the U3 region of the long terminal repeat. J Virol. 1986 Oct;60(1):1–11. [PMC free article] [PubMed] [Google Scholar]
- Yamamoto KR. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. [PubMed] [Google Scholar]
- Yazdanbakhsh K, Park CG, Winslow GM, Choi Y. Direct evidence for the role of COOH terminus of mouse mammary tumor virus superantigen in determining T cell receptor V beta specificity. J Exp Med. 1993 Aug 1;178(2):737–741. [PMC free article] [PubMed] [Google Scholar]
