ISOLATION AND CHARACTERIZATION OF A TYPE-II JC VIRUS FROM A BRAIN BIOPSY OF A PATIENT WITH PML

Brain tissue of a patient with multiple myeloma suffering from neurolo gical disorders similar to those seen in progressive multifocal leukoe ncephalopathy (PML) patients was evaluated for the presence of the pap ovavirus, JCV. Results from polymerase chain reaction (PCR) revealed t he presence of JCV with structural organization at the control region which is distinct from well-characterized isolates, ie Mad-1 and Mad-4 . The control region of the new isolate, named JCV(Phila-1), contains a 22 nucleotide insertion which separates the TATA box from the NF-1 r egulatory motif. Only 18 nucleotides of the insert are duplicated in t he second copy of the enhancer/promoter of the new isolate, which is 8 4 nucleotides in size. Results from a transcription assay indicate a m odest elevated level of JCV(Phila-1) early promoter activity compared to that of JCV(Mad-4) in glial cell lines. The basal and T-antigen-ind uced transcriptional activities of the JCV(Phila-1) late promoter was lower with respect to Mad-4 late gene activity in glial cells. Of part icular interest was the observation that in the cells producing the ea rly protein, T-antigen, JCV(Phila-1) DNA replicated more efficiently t hen the Mad-4 DNA. These results suggest that the alterations seen in the JCV(Phila-1) control region may differentially influence early and late gene expression and facilitate amplification of the viral genome in cells derived from the CNS.