Tovar Sepúlveda V A, Berdel B, Coffin J M, Reuss F U
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie F0400, 69120 Heidelberg, Germany.
Virology. 2000 Sep 15;275(1):98-106. doi: 10.1006/viro.2000.0491.
Expression of mouse mammary tumor virus (MMTV)-encoded superantigens in B lymphocytes are required for viral transmission and pathogenesis. Due to problems with detection and quantification of the superantigen protein, most reports about the mechanism of superantigen expression from the viral sag gene rely on the quantitative analysis of putative sag mRNAs. The description of multiple promoters as a source of putative sag mRNA has complicated the situation even further. All conclusions about the level of superantigen protein expression based on these data remain circumstantial. To test the effect of the glucocorticoid hormone dexamethasone on the total superantigen expression from an infectious MMTV provirus we used a quantitative assay that is based on a superantigen-luciferase fusion protein. MMTV gene expression from the major promoter in the 5' long terminal repeat (LTR) is strongly induced in the presence of glucocorticoid hormones. We now demonstrate that, in the presence of dexamethasone, sag gene expression is reduced despite increased transcription from the MMTV 5' LTR and increased amounts of putative sag mRNA initiated at the LTR promoter. These data show that the expression of the MMTV sag gene does not correlate with the activity of the major LTR promoter and thus differs from all other MMTV genes.
小鼠乳腺肿瘤病毒(MMTV)编码的超抗原在B淋巴细胞中的表达是病毒传播和发病机制所必需的。由于超抗原蛋白检测和定量存在问题,大多数关于病毒sag基因超抗原表达机制的报道依赖于对假定的sag mRNA的定量分析。将多个启动子描述为假定的sag mRNA来源,使情况更加复杂。基于这些数据得出的关于超抗原蛋白表达水平的所有结论仍然是间接的。为了测试糖皮质激素地塞米松对感染性MMTV前病毒总超抗原表达的影响,我们使用了一种基于超抗原-荧光素酶融合蛋白的定量测定法。在糖皮质激素存在的情况下,5'长末端重复序列(LTR)中主要启动子的MMTV基因表达被强烈诱导。我们现在证明,在地塞米松存在的情况下,尽管MMTV 5' LTR转录增加且从LTR启动子起始的假定sag mRNA量增加,但sag基因表达仍降低。这些数据表明,MMTV sag基因的表达与主要LTR启动子的活性不相关,因此与所有其他MMTV基因不同。