JC virus detection in the cerebrospinal fluid of AIDS patients with progressive multifocal leucoencephalopathy and monitoring of the antiviral treatment by a PCR method

Abstract

Twenty-four cerebrospinal fluid (CSF) samples from 19 AIDS patients with neurological signs were analysed by the polymerase chain reaction (PCR) for the presence of JC virus (JCV). Eleven of the 19 patients tested presented with progressive multifocal leucoencephalopathy (PML). Two specific JCV target sequences were used for the PCR analysis: a sequence specific for the T antigen genes from both BK virus (BKV) and JCV (PCR1) and a sequence specific for the large T antigen gene from JCV (PCR2). The JCV genome was detected in 10 of 11 patients with PML by the PCRl method and in all 11 patients by the PCR2 method. With samples from the eight patients without PML, one positive result was obtained with the PCRl method and this sample and another gave positive results with PCR2. Multiple CSF samples were collected from three patients with PML at different times, including after intrathecal cytarabine treatment, and were tested by the PCR2 method for the presence of the JCV genome. The PCR result became negative for two of the three patients during the cytarabine treatment. However, the absence of a PCR signal was not associated with clinical improvement in these patients. The PCR method is useful for the detection of JCV in CSF samples and in the diagnosis of PML. However, the application of PCR for monitoring the effect of treatment remains to be established.

Archetypal and rearranged sequences of human polyomavirus JC transcription control region in peripheral blood leukocytes and in cerebrospinal fluid.

“…From the literature (Matsiota-Bernard et al, 1997 ;Moret et al, 1993 ;Sugimoto et al, 1998) as well as from our data, the PCR method for the detection of JCV DNA in CSF samples appears to be undoubtedly useful for the diagnosis of PML. However, because of possible asymptomatic reactivation of JCV in the brain, further studies are required to assess the usefulness of other assays to use in combination with PCR such as quantitative PCR or TCR typing or even assays for anti-JCV antibody titration in CSF (Sindic et al, 1997).…”

“…The two others were from two AIDS patients with neurological disorders which, at the beginning, could be consistent with PML, but later were diagnosed for AIDS-dementia-complex (ADC) and neurotoxoplasmosis, respectively. In the literature, the detection of JCV DNA in CSF samples from two out of eight patients without PML has been reported but, in those cases, the TCR type was not assessed (Matsiota-Bernard et al, 1997). At variance with this observation, in our cases, a presumptive diagnosis of PML was done initially on the basis of clinical findings.…”

Latent and Persistent Polyomavirus Infection

“…The prevalence ranged from 0.22% to 8% of patients with neurologic symptoms and/or HIV infection Ferrante et al, 1997;Fong et al, 1995;Koralnik et al, 1999a;McGuire et al, 1995). In other studies, the rate of JCV DNA detection increased from 9% to 100% Dörries et al, 1998;Ferrante et al, 1998;Matsiota-Bernard et al, 1997). Most of the reports concentrated on HIV infection and other diseases at risk for PML.…”

Progressive multifocal leukoencephalopathy after autologous bone marrow transplantation and alpha-interferon immunotherapy

“…By polymerase chain reaction, JCV was found in a high percentage of HIVinfected patients with PML and also in the brains of AIDS patients without clinically evident PML. 15 It can persist at this site without causing demyelinating disease. In cases of severe immunodeficiency induced by aggressive chemotherapy, after organ transplantation or by HIV infection JCV might be reactivated and lead to the development of PML.…”