The mouse mammary tumour virus long terminal repeat encodes a type II transmembrane glycoprotein.

Korman, Alan J.; Bourgarel, P; T, Meo; Rieckhof, Gabrielle E.

doi:10.1002/j.1460-2075.1992.tb05242.x

Cited by 77 publications

(63 citation statements)

References 47 publications

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“…Within the highly variable COOH terminus of the sag gene multiple clones isolated from individual patients showed sequence differences from known strains of MMTV and from each other. However, all of the isolated clones were either identical or nearly identical to either the MMTV endogenous proviral sequences Mtv-8 (36,37) or Mtv-6 (38) and Mtv-1 (39,40) as shown in Fig. 4.…”

Section: Resultsmentioning

confidence: 80%

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Etkind

Stewart

Dorai

et al. 2004

Clinical Cancer Research

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Purpose: In a previous study, we had detected the presence of mouse mammary tumor virus (MMTV)-like envelope (ENV) gene sequences in both the breast tumors and non-Hodgkin's lymphoma tissue of two of our breast tumor patients who had been diagnosed simultaneously with both malignancies. The aim of this study was to determine if MMTV-like DNA sequences are present in the breast tumors and non-Hodgkin's lymphomas of additional patients suffering from both malignancies and if so to characterize these sequences in detail.Experimental Design: DNA was extracted from formalinfixed, paraffin-embedded tissue sample blocks of breast tumors and non-Hodgkin's lymphomas from patients suffering from both malignancies. A 250-bp region of the MMTV ENV gene and a 630-bp region of the MMTV long terminal repeat (LTR) open reading frame (ORF) that encodes the MMTV superantigen (sag) gene were amplified by PCR from the isolated DNA. Amplified products were analyzed by Southern blotting, cloned, and sequenced.Results: MMTV-like ENV and LTR sequences were detected in both the breast tumors and non-Hodgkin's lymphomas of 6 of 12 patients suffering from both malignancies. A novel mutant of the MMTV ENV gene was identified in these patients. Characterization of the MMTV-like LTR highly variable sag sequences revealed total or nearly total identity to three distinct MMTV proviruses from two different branches of the MMTV phylogenetic tree.Conclusions: The presence of MMTV-like ENV and LTR sequences in both the breast tumors and nonHodgkin's lymphomas of 6 additional patients suggests a possible involvement of these sequences in these two malignancies. MMTV-like LTR sequence homology to different MMTV proviruses revealed the presence of more than one strain of MMTV-like sequences in each individual suggesting the possibility of multiple infections in these patients.

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Section: Resultsmentioning

confidence: 80%

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Etkind

Stewart

Dorai

et al. 2004

Clinical Cancer Research

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“…MMTV infects B cells in the guts of newborn mice, and these cells express the virally encoded superantigen (Sag) at the plasma membrane in association with the major histocompatibility complex (MHC) class II protein (1,28). Sag is a type II transmembrane protein that is required for efficient transmission of milk-borne MMTV from the gut to the mammary gland (12,17,23). The Sag-MHC complex is recognized by entire classes of T cells bearing particular T-cell receptor (TCR) ␤ chains (18,28).…”

mentioning

confidence: 99%

C3H Mouse Mammary Tumor Virus Superantigen Function Requires a Splice Donor Site in the Envelope Gene

Mustafa

Lozano

Dudley

2000

J Virol

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Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is required for efficient milkborne transmission of virus from mothers to offspring. The mRNA used for Sag expression is controversial, and at least four different promoters (two in the long terminal repeat and two in the envelope gene) for sag mRNA have been reported. To determine which RNA is responsible for Sag function during milk-borne MMTV transmission, we mutated a splice donor site unique to a spliced sag RNA from the 5 envelope promoter. The splice donor mutation in an infectious provirus was transfected into XC cells and injected into BALB/c mice. Mice injected with wild-type provirus showed Sag activity by the deletion of Sag-specific T cells and induction of mammary tumors in 100% of injected animals. However, mice injected with the splice donor mutant gave sporadic and delayed T-cell deletion and a low percentage of mammary tumors with a long latency, suggesting that the resulting tumors were due to the generation of recombinants with endogenous MMTVs. Third-litter offspring of mice injected with wild-type provirus showed Sag-specific T-cell deletion and developed mammary tumors with kinetics similar to those for mice infected by nursing on MMTV-infected mothers, whereas the third-litter offspring of the splice donor mutant-injected mice did not. One of the fifth-litter progeny of splice donor mutant-injected mice showed C3H Sag activity and had recombinants that repaired the splice donor mutation, thus confirming the necessity for the splice donor site for Sag function. These experiments are the first to show that the spliced sag mRNA from the 5 envelope promoter is required for efficient milk-borne transmission of C3H MMTV.

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“…Total RNA was isolated using TRIZOL (Roche Diagnostics, Laval, Quebec, Canada), and first-strand cDNA was synthesized as follows. Total RNA (5 g) was reverse transcribed in the presence of 5 g of oligo(dT) [12][13][14][15][16][17][18] (Pharmacia Biotech), 20 U of RNAguard (Pharmacia Biotech), 2 mM dithiothreitol, 1 mM deoxynucleoside triphosphates, and 200 U of Moloney murine leukemia virus reverse transcriptase (GIBCO-BRL) for 2 h at 37°C. A 100-ng sample of total RNA was used for PCR amplification using 200 M each pair of primers under the following conditions: 1 min of denaturation at 94°C, 1.5 min of annealing at 55°C, and 1.5 min of extension at 72°C for 40 cycles.…”

Section: Methodsmentioning

confidence: 99%

“…MMTV vSags are type II integral glycoproteins having an extracellular carboxy terminus (7,18). Their primary structure shows a high degree of sequence conservation, except for a carboxy-terminal polymorphic region that imparts V␤ specificity (4,53).…”

mentioning

confidence: 99%

Alternative Proteolytic Processing of Mouse Mammary Tumor Virus Superantigens

Denis

Shoukry

Delcourt³

et al. 2000

J Virol

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Mouse mammary tumor viruses express a superantigen essential for their life cycle. It has been proposed that viral superantigens (vSags) require processing by prohormone convertases (PCs) for activity. We now observe, using a panel of mutant forms of potential PC cleavage sites and in vitro cleavage assays, that only the CS1 (position 68 to 71) and CS2 (position 169 to 172) sites are utilized by furin and PC5. Other members of the convertase family that are expressed in lymphocytes are not endowed with this activity. Furthermore, mutant forms of two different viral superantigens, vSag7 and vSag9, which completely abrogated in vitro processing by convertases, were efficient in functional presentation to responsive T-cell hybridomas. This effect was observed in both endogenous presentation and paracrine transfer of the vSag. Processing by convertases thus appears not to be essential for vSag function. Finally, we have identified the purified endosomal protease cathepsin L as another protease that is able to cleave convertase mutant vSag in vitro, yielding fragments similar to those detected in vivo, thus suggesting that proteases other than convertases are involved in the activation of vSags.

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The mouse mammary tumour virus long terminal repeat encodes a type II transmembrane glycoprotein.

Cited by 77 publications

References 47 publications

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

C3H Mouse Mammary Tumor Virus Superantigen Function Requires a Splice Donor Site in the Envelope Gene

Alternative Proteolytic Processing of Mouse Mammary Tumor Virus Superantigens

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