Infection with JC virus and possible dysplastic ganglion-like transformation of the cerebral cortical neurons in a case of progressive multifocal leukoencephalopathy

Infection of the cerebral cortical neurons with JC virus (JCV) with possibl e dysplastic ganglion-like alteration of the infected neurons found in a ca se of progressive multifocal leukoencephalopathy (PML) is described. The pa tient was a 21-year-old man with common variable immunodeficiency who died of PML after a 9-month clinical course. Ar autopsy, the white matter of the cerebrum, brainstem, cerebellum, and spinal cord exhibited extensive demye lination and necrosis. Numerous inclusion-bearing oligodendrocytes and biza rre astrocytes were found. In the occipital and temporal cortex, thick band like aggregates of dysplastic ganglion-like cells (DGLCs) were found. These DGLCs showed immunohistochemical properties of neurons, and nuclei of some DGLCs were immunoreactive for large T antigen of SV40/JCV and p53, but not for capsid protein JCV VP1. In situ hybridization for mRNA of JCV large T antigen revealed positive signals in the nuclei of some DGLCs. These result s indicate that JCV infected neurons and it is suggested that binding of th e large T antigen with cellular proteins could have resulted in the dysplas tic, ganglion cell-like change of the infected neurons, although the possib ility that the aggregates of DGLCs represent a pre-existent malformative le sion of the cortex cannot be excluded completely.