Detection of JC virus DNA fragments but not proteins in normal brain tissue
Georgina Perez-Liz1, Luis Del Valle, Antonio Gentilella
1Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19122, USA.
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.
Insights
The human neurotropic JC virus (JCV) DNA fragments were found in the brains of healthy individuals, suggesting the brain may be a site for JCV latency. This could lead to progressive multifocal leukoencephalopathy (PML) if the immune system weakens.
Area of Science:
- Neurovirology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by JC virus (JCV) in immunocompromised patients.
- JCV is thought to travel from the kidneys to the brain, where it destroys glial cells, leading to PML.
Purpose of the Study:
- To investigate the hypothesis that JCV may exist in a latent state within the brains of immunocompetent individuals without neurological conditions.
Main Methods:
- Examined JCV DNA and protein presence in five brain regions of seven immunocompetent individuals using gene amplification and immunohistochemistry.
- Utilized laser-capture microdissection to identify specific cell types harboring JCV DNA.
Main Results:
- JCV DNA fragments were detected in various brain regions of healthy individuals.
- JCV DNA was found in oligodendrocytes and astrocytes, but not neurons.
- No viral proteins were expressed in any of the examined brains.
Conclusions:
- The presence of JCV DNA in non-PML brains indicates JCV can access all brain regions in immunocompetent individuals.
- This suggests the brain could be a potential site for JCV latency.
- Reactivation of JCV and subsequent demyelination (PML) may occur if immune function is compromised.
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