Neuroimmune regulation of JCV by immune mediators in glial cells

The human polyomavirus JC (JCV) is a small DNA virus responsible for the initiation of progressive multifocal leukoencephalopathy (PML), an often lethal disease of the brain characterized by lytic infection of oligodendrocytes in the central nervous system (CNS). Patients undergoing immune modulatory therapies for the treatment of autoimmune diseases such as multiple sclerosis, and individuals with an impaired-immune system, most notably AIDS patients, are in the high risk group of developing PML. Previous studies suggested that soluble immune mediators secreted from PBMCs inhibited viral genomic replication. However little is known regarding the molecular mechanism of this regulation. Here we investigated the impact of conditioned media (CM) from activated PBMCs on viral replication and gene expression by molecular virology techniques. Our data showed that viral gene expression as well as viral replication was suppressed by the CM. Further studies revealed that soluble immune mediators from PBMCs possessed a dual control on T-antigen expression at transcription and post-transcription level. These observations demonstrate a novel role of immune mediators in regulation of JCV gene expression, and provide a new avenue of research to understand molecular mechanism of viral reactivation in patients who are at risk of developing PML. [edited by author]