Ritrovamento, caratterizzazione molecolare ed analisi di espressione del virus JC nei tumori cerebrali umani

Human Polyomaviruses can establish a latent infection in the kidney of up to 80% of the adult population worldwide and JCV induces progressive multifocal leukoencephalopathy (PML) in immunodeficient individuals. Recently several mounting evidences point to the association of Polyomaviruses with human cancer, more notably brain tumors. To further investigate this hypothesis, brain biopsy tissue, cerebrospinal fluid (CSF) and peripheral blood (PB) were collected from 40 Italian individuals suffering of brain tumors. Using PCR we investigated the presence of LT-Antigen (LT) DNA fragment common to JCV, BKV and SV40. JCV DNA was found in 37.5% of tumor tissues, 11.1% of CSF and 5.4% of PB, whereas BKV DNA was found in 20 % of biopsies and SV40 was not detected in the studied samples. Since 55.5% of tissues from glioblastomas and 37.5% from meningiomas were positive for JCV LT DNA, we focused our attention on this viral agent. The study of JCV genotype distribution, based on sequencing of VP1, showed that mostly of the amplified strains were JCV type 1, whereas the analysis of TCR nucleotide sequence indicated the IR (Mad 4) organization as the most frequent. The late gene Agnoprotein DNA was amplified in 7 biopsies, 6 of which were glioblastomas. Moreover, we found, by means of RT-PCR, that LT-antigen was actively transcribed in 60 % of the JCV - positive tested biopsies. Altogether, the results from gene amplifications and gene expression analysis of the various brain tumor samples add further elements in favor of the possible association of JCV with CNS tumors, and especially with glioblastoma.