Atwood W J, Wang L, Durham L C, Amemiya K, Traub R G, Major E O
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurovirol. 1995 Mar;1(1):40-9. doi: 10.3109/13550289509111009.
The human polyomavirus, JCV, is the etiologic agent of the fatal central nervous system demyelinating disease, progressive multifocal leukoencephalopathy. Progressive multifocal leukoencephalopathy occurs most frequently in patients with underlying immunosuppressive disorders and is the direct result of virus multiplication in oligodendrocytes, the myelin producing cell in the central nervous system. In this report we test the ability of cellular activation signals to modulate expression of the JCV genome in either transfected or infected human fetal glial cells. In addition, we analyze the binding of nuclear proteins isolated from untreated and cytokine treated human fetal glial cells to transcription factor binding sites in the JCV regulatory region. In contrast to the effects of cellular activation on the expression of the HIV-1 promoter in these cells, none of the cellular activators tested increased expression of JCV. The cytokine, TNF-alpha, increased binding of NF kappa B (p50/p65) to a JC NF kappa B site but did not modulate the binding of nuclear proteins to the overlapping NF-1/AP1 region of the JCV enhancer. When taken together these results suggest that the response of JCV to cellular activation signals may be fundamentally different from the response of HIV-1 to these signals in human fetal glial cells and that the JC NF kappa B site may not be required for JCV gene expression or multiplication in vivo.
人类多瘤病毒JCV是致命的中枢神经系统脱髓鞘疾病——进行性多灶性白质脑病的病原体。进行性多灶性白质脑病最常发生于患有潜在免疫抑制性疾病的患者，是病毒在少突胶质细胞（中枢神经系统中产生髓磷脂的细胞）中增殖的直接结果。在本报告中，我们测试了细胞激活信号调节转染或感染的人胎儿神经胶质细胞中JCV基因组表达的能力。此外，我们分析了从未经处理和经细胞因子处理的人胎儿神经胶质细胞中分离出的核蛋白与JCV调控区域中转录因子结合位点的结合情况。与这些细胞中细胞激活对HIV-1启动子表达的影响相反，所测试的细胞激活剂均未增加JCV的表达。细胞因子TNF-α增加了NF-κB（p50/p65）与JC NF-κB位点的结合，但未调节核蛋白与JCV增强子重叠的NF-1/AP1区域的结合。综合这些结果表明，JCV对细胞激活信号的反应可能与HIV-1在人胎儿神经胶质细胞中对这些信号的反应存在根本差异，并且JC NF-κB位点可能不是JCV基因在体内表达或增殖所必需的。
