NFAT4 Is Required for JC Virus Infection of Glial Cells

• DOI: 10.1128/jvi.01456-06
• Publication Date: 2006-11-27T23:43:39Z
• Authors: Kate Manley; Bethany A. O'Hara; Gretchen V. Gee; Carl P. Simkevich; John M. Sedivy; Walter J. Atwood
• Keywords: NFAT; JC Virus; Demyelinating disease; Chromatin immunoprecipitation

The human polyomavirus JC virus (JCV) infects 70% of the population worldwide. In immunosuppressed patients, JCV infection can lead to progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease central nervous system (CNS). majority PML cases occur in setting immunodeficiency (HIV) infection, and it has been suggested that link between HIV development is part related production numerous cytokines CNS during infection. To examine expression inflammatory we tested an anti-inflammatory compound, cyclosporine A (CsA), for its ability block glial cells. We found CsA inhibited by preventing activation transcription factor nuclear activated T cells 4 (NFAT4). Luciferase reporter assays chromatin immunoprecipitation revealed NFAT4 directly bound promoter was important both early late transcription. addition, viral gene products increased NFAT activity further aid necessity suggests calcium signaling are required CNS.