Characterisation of BKV strains detected in spinal fluids of Spanish neurological patients

Family Polyomaviridae contains the widely distributed human polyomaviruses BK (BKV) and JC (JCV). Whereas JCV is the etiologic agent of multifocal progressive leukoencephalopathy in AIDS patients, BKV produces nephropathy and ureteral stenosis in renal tr ansplant recipients and hemorrhagic cystitis in bone marrow transplant recipients. BKV neurological involvement is rare and has been very poorly described. BKV genome contains the conserved early and late regions and the hypervariable noncoding control re gion (NCCR). The early region codes for the tumour antigens T and t and the late region codes for the capside proteins VP1, supposedly implicated in BKV tropism, VP2 and VP3 and the agnoprotein. The NCCR contains the origin of replication, the TATA BOX, T -Antigen binding sites and the promoter and enhancer for the early and late regions. The prototypal form of the NCCR is called Archetype and it is arbitrarily divided into regions O (142 base pairs -bp-), P (68 bp), Q (39 bp), R (63 bp) and S (63 bp). Rea rranged configurations produced by duplications, deletions or insertions could be associated to altered replication, transcription or pathology. The characterisation of the BKV NCCR from the Cerebrospinal Fluids (CSF), serums and urines from 18 neurologic ally affected patients has been performed by the applicant as part of her doctoral thesis and archetypal and different rearranged forms have been found. The aims of the stay include: 1. The characterisation of other regions of the BKV genome such as VP1 that could clarify the mechanism of pathogenesis of these strains. 2. The infection of permissive cells with the BKV PCR positive CSFs to attempt the recovery of infectious particles, including neuroblastoma cell lines in order to evaluate their neurotro prism. 3. The comparison of the early and late promoter activity of the different NCCR variants detected in the CSF with those of the archetypal strain (WW).