EVALUATION OF THE ROLE OF CYTOKINE ACTIVATION IN THE MULTIPLICATION OF JC VIRUS (JCV) IN HUMAN FETAL GLIAL-CELLS

The human polyomavirus, JCV, is the etiologic agent of the fatal centr al nervous system demyelinating disease, progressive multifocal leukoe ncephalopathy. 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 w e test the ability of cellular activation signals to modulate expressi on of the JCV genome in either transfected or infected human fetal gli al cells. In addition, we analyze the binding of nuclear proteins isol ated from untreated and cytokine treated human fetal glial cells to tr anscription factor binding sites in the JCV regulatory region. In cont rast to the effects of cellular activation on the expression of the HI V-1 promoter in these cells, none of the cellular activators tested in creased 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 t he binding of nuclear proteins to the overlapping NF-1/AP1 region of t he JCV enhancer. When taken together these results suggest that the re sponse of JCV to cellular activation signals may be fundamentally diff erent 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 gen e expression or multiplication in vivo.