p53 and proliferating cell nuclear antigen expression in JC virus-infected cells of progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS) caused by infection with JC papova virus (JCV), is characterized by marked atypical changes in the glial cells. The JCV T protein binds cellular p53 (a tumor suppressor gene product), which as a result loses its normal down regulating influence on the cell cycle. We hypothesized that this binding would stabilize p53 and prolong its half life, leading to its immunohistochemical detection. To prove our theory combined JCV DNA:DNA in situ hybridization (ISH) and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) as well as p53/GFAP double IHC were performed on routinely processed sections of five brains obtained at autopsy and two cerebral biopsy specimens from seven patients with PML. All specimens showed JCV infected oligodendrocytes and bizarre looking astrocytes that immunostained strongly for p53. In addition, because loss of p53 function results in proliferating cell nuclear antigen (PCNA) overexpression PCNA/GFAP double IHC was carried out, and a positive immunoreaction was obtained in JCV infected cells in the two biopsy specimens. The evidence of p53 immunoreactivity in JCV harboring glial cells seems to indicate a link between the JCV induced stabilization/inactivation of p53 and the striking tumorlike glial changes seen in PML. Proliferating cell nuclear antigen overexpression in these cells further supports this pathogenetic construct.
Ariza
A
A
Department of Anatomic Pathology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Spain.
Mate
J L
JL
Fernández-Vasalo
A
A
Gómez-Plaza
C
C
Pérez-Piteira
J
J
Pujol
M
M
Navas-Palacios
J J
JJ
D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007577:JC Virus / Q000235:genetics; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53