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Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal
C Tornatore1, J R Berger, S A Houff
1Section of Molecular Virology, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
Abstract:
Progressive multifocal leukoencephalopathy (PML) results from lytic infection of oligodendrocytes by JC virus (JCV). Although JCV has been identified in mononuclear cells in bone marrow and hematogenous dissemination of the virus to the central nervous system has been suspected, JCV has never been clearly demonstrated in the peripheral circulation. Using polymerase chain reaction technology, we examined peripheral lymphocytes of 19 patients with brain biopsy-proven PML for the JCV genome. Two non-PML control groups, consisting of 26 patients seopositive for human immunodeficiency virus type 1 (HIV-1) and 30 immunocompetent patients with Parkinson's disease, were also examined for the presence of the JCV genome in lymphocytes. Cerebrospinal fluid from 10 patients with PML was examined for the presence of the JCV genome as well. The JCV genome was detected in the lymphocytes of 89% (17) of the patients with PML, 38% (10) of the HIV-1-seropositive patients without PML, and none of the patients with Parkinson's disease. Sequencing of the JCV regulatory region from the lymphocytes of three patients revealed the prototype MAD-1 strain of JCV in one patient with PML, a MAD-4 strain in a second patient with PML, and a slightly modified MAD-4 strain in an HIV-1-positive patient without PML. Only 3 of 10 patients with PML who had JCV detected in lymphocytes had the JCV genome in their cerebrospinal fluid. These results demonstrate that the JCV genome can be found in circulating lymphocytes from patients with PML and suggest that lymphocytes are an important vector for hematogenous dissemination of JCV to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
JC virus (JCV) DNA was found in the lymphocytes of most progressive multifocal leukoencephalopathy (PML) patients, suggesting lymphocytes spread JCV to the brain. This finding aids understanding of PML pathogenesis.
Area of Science:
- Neurovirology
- Immunology
- Molecular Biology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC virus (JCV) lytic infection of oligodendrocytes.
- Hematogenous spread of JCV to the central nervous system is suspected, but JCV has not been clearly detected in peripheral circulation.
- Oligodendrocytes are the myelin-producing cells in the central nervous system.
Purpose of the Study:
- To investigate the presence of the JCV genome in peripheral lymphocytes of PML patients.
- To determine if lymphocytes serve as a vector for JCV dissemination to the central nervous system.
- To compare JCV detection rates in PML patients with HIV-1-seropositive and immunocompetent control groups.
Main Methods:
- Polymerase chain reaction (PCR) was used to detect the JCV genome in peripheral lymphocytes.
- Peripheral lymphocytes from PML patients, HIV-1-seropositive controls, and Parkinson's disease controls were analyzed.
- Cerebrospinal fluid (CSF) from PML patients was also tested for the JCV genome.
- Sequencing of the JCV regulatory region was performed on positive samples.
Main Results:
- The JCV genome was detected in 89% of PML patients' lymphocytes, 38% of HIV-1-seropositive controls, and 0% of Parkinson's disease controls.
- Different JCV strains (MAD-1, MAD-4) were identified in PML patients and one HIV-1-positive patient.
- Only 30% of PML patients with JCV in lymphocytes also had JCV detected in their CSF.
Conclusions:
- The JCV genome is present in circulating lymphocytes of PML patients.
- Peripheral lymphocytes are likely a significant vector for the hematogenous dissemination of JCV to the central nervous system.
- Detection of JCV in lymphocytes offers a potential diagnostic marker and insight into PML pathogenesis.