A transcriptionally defective long terminal repeat within an endogenous copy of mouse mammary tumor virus proviral DNA

Abstract

Mouse mammary tumor virus proviral DNA is endogenous to most inbred strains of mice but in many strains is not transcriptionally active. This inactivity may be due to defects in the proviruses themselves or to position effects mediated by DNA sequences flanking the proviral units. The transcriptional competence of long terminal repeats (LTRs) derived from endogenous proviral DNA at genetic loci Mtv-8, Mtv-9, and Mtv-17 of the C57BL/ 6 mouse strain was examined with a transient transfection assay in which gene expression was monitored by expression of chloramphenicol acetyltransferase. LTRs from Mtv-8 and Mtv-9 were able to direct glucocorticoid-induced chloramphenicol acetyltransferase expression in this assay, while the LTR from Mtv-17 was only about 5% as effective. Analysis of chimeric LTRs indicated that the glucocorticoid-inducible transcriptional enhancer element within the Mtv-17 LTR is active when linked to a functional promoter from Mtv-8, whereas the promoter from Mtv-17 is defective in directing hormone-induced gene expression, even when linked to the Mtv-8 glucocorticoid-responsive enhancer. The DNA sequence of transcriptional control regions of the LTRs of all three endogenous proviral units was determined; this analysis revealed that the source of the defect in Mtv-17 is a single G-to-A transition at position-75 with respect to the site of transcription initiation that resides within the previously defined binding site for the transcription factor nuclear factor 1. Competition experiments with a gel electrophoresis mobility shift assay indicated that the affinity of nuclear factor 1 for DNA derived from Mtv-17 is significantly less than for comparable sequences derived from Mtv-8.

Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen.

“…Comparison of the Mtv proviruses carried by these strains suggests two candidates, Mtv-6 and Mtv-7, based on their presence in C3H/BiDa and absence in C57BK/cdJ mice ( Table 2). Mtv-17 is not considered because a mutation in its LTR most likely prevents expression (45), and no deletion of T cells bearing the expected V/3 specificity has been found (44). Anti-polyoma T cells in the resistant C57BK/cdJ mouse would therefore be predicted to express either V/33 if Pyv s were Mtv-6 sag, or VB6 and/or V/37 if Pyv s were Mtv-7 sag.…”

Mouse mammary tumor virus proviruses in T-cell lymphomas lack a negative regulatory element in the long terminal repeat

“…The EL4 clones 2 and 13 have an A at position 1120 ( Fig. 1) which reportedly reduces NF1 binding (19).…”

“…Many of these differences are located between the deletion and the TATA box around position 1160 ( Fig. 1) and may affect the proximal glucocorticoid receptor-binding site (1) or the NFl-binding site (1,5,19). The EL4 clones 2 and 13 have an A at position 1120 ( Fig.…”

The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire.

“…Mtu17 also belongs in this family by virtue of its specificity for T cells bearing VJ~I 1, and -12. However, the published sequence of vSAGt7 is slightly different from vSAG8, -9, and -11 (42,49) and homologous to vSAG23, which is specific for VJ37 (35). Although vSAG23 only stimulated T cell hybrids bearing VI37 (35), it is possible that it induces the deletion o f T cells Why vSAG8 Deletes V~7-bearing T Cells.…”