POLYMORPHISM ANALYSIS OF THE JCV MAJOR CAPSID PROTEIN AND TRANSCRIPTIONAL CONTROL REGION REARRANGEMENTS IN HIV POSITIVE PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY PATIENTS UNDER HIGHLY ACTIVE ANTI-RETROVIRAL THERAPY

Before the introduction of HAART, PML was estimated to affect up to 7% of AIDS patients and lead them to fatal outcome in less than 1 year. In the era of HAART, the incidence of many AIDS related opportunistic infections has been dramatically decreased and it has been shown that about 50% of the HAART treated PML patients had a survival time significantly prolonged, in comparison to the classical survival time. To explain the change in the prognosis of PML patients, it could be hypothesized that specific JCV adjustment in the viral genome could occur. For this purpose, we investigated the genomic organization of JCV strains from HAART treated and untreated PML patients. We analyzed DNA sequences corresponding to 25 VP1 and 28 TCR JCV regions in HAART untreated PML patients, of 17 HAART treated PML patients and of 30 healthy individuals. In HAART untreated PML patients we found that 52% and 44 % of amplified JCV were type 1 and type 2, respectively. In HAART treated PML patients 59% of the amplified JCV were classified as type 1, 23% as type 2 and 18% were type 4, without differences between long and short survivors. In both groups we found TCR with unique and extensive archetype-derived rearrangements. An archetype organization of TCR was detected in two long survivor PML patients. The data obtained in this study indicate a change in the distribution of JCV genotypes in HAART treated in comparison to untreated PML patients. The finding, for the first time, of an archetype TCR in two long survivor HAART treated PML is of particular relevance.