cyclin-d1 and Leukoencephalopathy--Progressive-Multifocal

Both SV40 and JC virus (JCV) appropriate the host cell replicative machinery to attend to their own reproductive needs. SV40 large T antigen is able to induce the expression of cyclins A, B1, and E (but not of cylin D1) in transfected diploid cells. Whether JCV infection influences cyclin expression in a similar fashion in the setting of progressive multifocal leukoencephalopathy (PML) remains unknown. Brain lesions from 7 PML cases (4 autopsies and 3 biopsies) were immunohistochemically investigated for the expression of Ki-67 and cyclins A, B1, and D1. All 7 cases showed strong positivity for Ki-67 and cyclins A and B1 in JCV-infected oligodendrocytes and astrocytes, the nuclear immunolocalization of cyclin A being in strong contrast to the cytoplasmic distribution of cyclin B1. No immunostaining for cyclin D1 was obtained in any of the 7 cases. These findings suggest that JCV infection is associated with overexpression of Ki-67 and cyclins A and B1 in PML host glial cells. Since cyclin changes in JCV-infected cells recapitulate SV40 T antigen-associated cyclin fluctuations, it appears reasonable to think that JCV T antigen shares some of the previously described capabilities of SV40 T antigen to alter cyclin expression for the sake of viral replication.

Topics: Acquired Immunodeficiency Syndrome; Adult; Brain; Cyclin A; Cyclin B; Cyclin B1; Cyclin D1; Cyclins; DNA, Viral; Humans; Immunocompromised Host; Immunoenzyme Techniques; In Situ Hybridization; JC Virus; Ki-67 Antigen; Leukoencephalopathy, Progressive Multifocal; Male; Middle Aged; Papillomavirus Infections; Tumor Virus Infections