This study investigates cellular alterations and pathogenesis induced by the human polyomavirus, JC virus (JCV) in experimental animals and human tissues. JCV causes the human CNS demyelinating disease, progressive multifocal leukoencephalopathy (PML) and induces brain tumor formation in experimental animals. Immunohistochemical studies have focused on JCV infection of and/or interacting influence on astrocytes, vascular endothelial cells (EC) and neurons. JCV-infected astrocytes were observed in most PML cases examined, with one non-AIDS PML case exhibiting extensive infection of basal ganglia astrocytes. Comparative evaluation of astrocytic markers revealed an apparent progression from early-onset loss of GFAP expression in some astrocytes, to increased expression of vimentin in astrocytes outside of lesion areas and in early focal clusters. GFAP-positive reactive astrocytes surrounded more advanced lesions with some cells double-labeled for GFAP and vimentin. Lesion area vascular alterations were suggested by increased expression of basement membrane components laminin and collagen IV while EC expression of Factor VIII and ICAM-1 was similar to control brains. Cerebellar internal granular layer changes were present in some cases with apparent loss of granule neurons. This was also noted in the hamster model of JCV brain infection in addition to infection and neoplasia of granule neurons with accompanying astrocytosis. Recent efforts include the development of a mouse model to examine the influence of the HIV TAT protein on JCV-induced pathogenesis. Studies indicate that JCV is expressed in subependymal and subpial cells 3 to 15 days after intracerebral inoculation into newborn mice and in some kidney cells in intraperitoneally-inoculated animals. JCV expression is currently being examined in JCV-inoculated transgenic mice carrying SV40- TAT gene sequences.
