P53 AND PROLIFERATING CELL NUCLEAR ANTIGEN EXPRESSION IN JC VIRUS-INFECTED CELLS OF PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Progressive multifocal leukoencephalopathy (PML), a demyelinating dise ase of the central nervous system (CNS) caused by infection with JC pa pova virus (JCV), is characterized by marked atypical changes in the g lial cells. The JCV T protein binds cellular p53 (a tumor suppressor g ene product), which as a result loses its normal down regulating influ ence on the cell cycle. We hypothesized that this binding would stabil ize p53 and prolong its half life, leading to its immunohistochemical detection. To prove our theory combined JCV DNA:DNA in situ hybridizat ion (ISH) and glial fibrillary acidic protein (GFAP) immunohistochemis try (IHC) as well as p53/GFAP double MC were performed on routinely pr ocessed sections of five brains obtained at autopsy and two cerebral b iopsy specimens from seven patients with PML. All specimens showed JCV infected oligodendrocytes and bizarre looking astrocytes that immunos tained strongly for p53. In addition, because loss of p53 function res ults in proliferating cell nuclear antigen (PCNA) overexpression PCNA/ GFAP double MC was carried out, and a positive immunoreaction was obta ined in JCV infected cells in the two biopsy specimens. The evidence o f p53 immunoreactivity in JCV harboring glial cells seems to indicate a link between the JCV induced stabilization/inactivation of p53 and t he striking tumorlike glial changes seen in PML. Proliferating cell nu clear antigen overexpression in these cells further supports this path ogenetic construct. Copyright (C) 1994 by W.B. Saunders Company