Molecular biology and immunoregulation of human neurotropic JC virus in CNS

Abstract

The human polyomavirus, JC virus (JCV), provides an excellent model system to investigate the reciprocal interaction of the immune and nervous systems. Infection with JCV occurs during childhood and the virus remains in the latent state with no apparent clinical symptoms. However, under immunosuppressed conditions, the virus enters the lytic cycle and upon cytolytic destruction of glial cells, causes the fatal demyelinating disease of the central nervous system (CNS), named progressive multifocal leukoencephalopathy (PML). In this short review, we discuss the molecular pathogenesis of PML by highlighting the role of the immune system in modulating JCV gene activation and replication, and the latency/ reactivation of this virus upon immunosuppression. Further, due to the higher incidence of PML among AIDS patients, we further elaborate on the cross-talk between JCV and HIV-1 by direct and indirect pathways that lead to enhanced expression of the JCV genome.

Patients With an Acute Zonal Occult Outer Retinopathy–like Illness Rapidly Improve With Valacyclovir Treatment

“…29, 34 Thus, a much greater diversity of phenotypes may exist for viral disease than was previously appreciated due to more sensitive laboratory detection methods. 34–36 …”

The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases

“…The ability of the JC virus to infect cells within the CNS and cause PML is dependent on the virus's ability to rearrange its transcription control region that facilitates the binding of appropriate DNA binding transcription factors that regulate gene expression [1,19,20]. Patients with PML who have JC virus isolated from the CNS (primary virus isolates) reveal unique tandem repeats in the transcription control region that increases the efficiency of viral replication in the presence of transcription factors.…”

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

“…However, binding itself does not appear to be a critical step in establishing productive infection. The ability of JCV to infect CNS glial cells (which correlates well with its pathogenic potential for causing PML) is contingent upon rearrangement of the viral transcription control region (TCR) and upon intracellular DNA binding proteins that direct gene expression from the rearranged TCR (47,51).…”