Progressive multifocal leukoencephalopathy in human immunodeficiency virustype 1-infected patients: absence of correlation between JC virus neurovirulence and polymorphisms in the transcriptional central region and the major capsid protein loci

Progressive multifocal leukoencephalopathy (PML) is a rapidly fatal demyeli nating disease of the central nervous system related to JC polyomavirus (JC V) replication in oligodendrocytes, PML usually occurs in immunocompromised individuals, especially in the setting of AIDS. Administration of highly a ctive anti-retroviral therapy (HAART) may improve survival prognosis in som e, but not all, patients with AIDS-related PML, This observation might be e xplained by the outgrowth of some JCV variants of increased fitness. To eva luate this hypothesis, two subgroups of five patients with AIDS-related PML , started on HAART after PML diagnosis, were analysed. The non-responder (N R) patients died rapidly despite HAART, while responders (R) had a positive outcome and were still alive. JCV DNA was extracted from cerebrospinal flu id biopsies and two regions of the genome were analysed, the transcriptiona l control region (TCR) and the major capsid protein gene (VP1), Both region s show different degrees of polymorphism and are recognized as evolving ind ependently. Sequence analysis demonstrated that (i) extensive TCR rearrange ments were present in both subgroups of patients, (ii) VP1 sequence polymor phisms could be identified in the BC loop, suggesting the absence of immune selection, and (iii) no genomic marker for ICV specific neurovirulence cou ld be identified in the TCR and VP1 loci.