Semiquantitative detection of JCV‐DNA in peripheral blood leukocytes from HIV‐1‐infected patients with or without progressive multifocal leukoencephalopathy

Abstract

Progressive Multifocal Leukoencephalopathy (PML) is a severe and fatal demyelinating disease that occurs especially in HIV-infected patients. It has been suggested that JC virus (JCV) migrates in peripheral blood leukocytes from the kidney to the central nervous system where it initiates demyelination. To investigate the physiopathological role of the peripheral blood virus in the development of PML, the prevalence of JCV infection and the levels of JCV DNA load were evaluated in peripheral blood leukocytes or mononuclear cells of 10 AIDS patients at the time of onset of PML symptoms, and in 150 non-PML HIV-1-infected patients using a semiquantitative PCR and ELISA-hybridization assay. In PML-AIDS patients, 60% (6/10) were positive for JCV-DNA detection in peripheral blood cells compared with 26% (13/50) and 18% (18/100) positive for non-PML HIV-infected control patients with CD4+ T lymphocyte counts below and above 200.10(6) /l, respectively (60 vs. 26%, P = 0.06; 60 vs. 18%; P = 0.007). The prevalence of JCV infection in the peripheral blood cells taken from controls appeared to be independent of the CDC stage of infection and CD4+ T lymphocyte counts. The predictive positive value of a positive JCV DNA PCR in peripheral blood cells for the diagnosis of PML in an HIV-infected patient was 16% whereas the predictive negative value was 96%. The levels of circulating JCV DNA load, ranging from 1.69 to 2.53 log of copies per 10(6) cells, did not differ between patients at time of PML symptoms onset and controls, and appeared to be independent of the clinical and the biological status in control patients. The findings do not indicate any significant JCV genomic replication activity in peripheral blood cells at the onset of PML disease, and suggest that JCV replication markers in the systemic compartment would not be valuable for predicting the development of PML in AIDS patients.