Detection of JC virus DNA fragments but not proteins in normal brain tissue

Abstract

Objective Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the white matter affecting immunocompromised patients that results from the cytolytic destruction of glial cells by the human neurotropic JC virus (JCV). According to one model, during the course of immunosuppression, JCV departs from its latent state in the kidney and after entering the brain, productively infects and destroys oligodendrocytes. The goal of this study was to test the hypothesis that JCV may reside in a latent state in a specific region of the brains of immunocompetent (non‐PML) individuals without any neurological conditions. Methods Gene amplification was performed together with immunohistochemistry to examine the presence of JCV DNA sequences and expression of its genome in five distinct regions of the brain from seven immunocompetent non‐PML individuals. Results Although no viral proteins were expressed in any of these cases, fragments of the viral DNA were present in various regions of normal brain. Laser‐capture microdissection showed the presence of JCV DNA in oligodendrocytes and astrocytes, but not in neurons. Interpretation The detection of fragments of viral DNA in non‐PML brain suggests that JCV has full access to all regions of the brain in immunocompetent individuals. Thus, should the immune system become impaired, the passing and/or the resident virus may gain the opportunity to express its genome and initiate its lytic cycle in oligodendrocytes. The brain as a site of JCV latency is a possibility. Ann Neurol 2008; 64:379–387