ANALYSIS OF CELLULAR FACTORS AFFECTING RETROVIRUS INFECTION AND GROWTH

已知ETS应答元件参与逆转录病毒的长 末端重复序列（LTR）依赖性在动物和人中表达， 一直在表征ERF作为抗病毒药物的潜力，并且 其对ETS依赖性病毒功能的影响。 表达 ETS 1/ETS 2依赖性转录抑制基因ERF未能阻断 促红细胞生成素（EPO）依赖性增殖的ME 26感染， 表达gag-myb-ets的FDC-P2细胞。 因为我们之前已经证明， ERF可抑制ME 26依赖gag-myb-ets的细胞毒作用， 降低小鼠白血病病毒依赖性 ME 26病毒RNA在NIH 3 T3成纤维细胞中的表达，我们的结果可能 表明融合癌基因通过不同的机制起作用，或 需要成纤维细胞和FDC-P2中不同水平的ETS功能 细胞 与对ERF缺乏反应相反，FDC-P2（ME 26）细胞 EPO的增殖被一种 表达ERG-B/FLI-1的逆转录病毒构建体，但不是通过一个表达 ERF的抑制结构域融合到 ERG-B/FLI-1。 表达ERG-B/FLI-1的细胞显示表达增加 促红细胞生成素受体特异性mRNA和β-珠蛋白mRNA， 在从IL-3转变为IL-4的48小时内经历凋亡性细胞死亡。 含EPO的培养基。

ETS-responsive elements are known to be involved in retroviral long terminal repeat (LTR)- dependent expression in animals and man, and we have been characterizing the potential for ERF as an antiviral agent, and its effect on ETS-dependent viral functions. Expression of the ETS1/ETS2-dependent transcriptional inhibitor gene, ERF, failed to block erythropoietin (EPO)- dependent proliferation of ME26-infected, gag-myb-ets-expressing FDC-P2 cells. Since we had previously shown that ERF could inhibit the gag-myb-ets-dependent ability of ME26 to abrogate the serum-dependence and reduce the murine leukemia virus-dependent expression of ME26 viral RNA in NIH3T3 fibroblasts, our results may suggest that the fusion oncogene acts through different mechanisms, or requires different levels of ETS function in fibroblasts and FDC-P2 cells. In contrast to the lack of response to ERF, FDC-P2 (ME26) cell proliferation in EPO was blocked by superinfection with an ERG-B/FLI-1-expressing retroviral construct, but not by one expressing the inhibitory domain of ERF fused to the DNA-binding domain of ERG-B/FLI-1. Cells expressing ERG-B/FLI-1 showed increased expression of erythropoietin receptor-specific mRNA and beta-globin mRNA, but underwent apoptotic cell death within 48 hours of the shift from IL-3 to EPO-containing media.