Regulatory sequences of SV40 variants isolated from patients with progressive multifocal leukoencephalopathy

Abstract

Variants of the simian polyomavirus SV40 have been associated in humans with a small number of cases of progressive multifocal leukoencephalopathy (PML). Genomic regulatory regions of two independent isolates, SVPML-1 and -2 [L.P. Weiner et al., N. Engl. J. Med. 286, 385 (1972)], were analyzed to determine if they had acquired any sequences that are present in the genome of the human polyomavirus JC (JCV), the primary causative agent of PML. As compared to SV40 DNA, 83% of SVPML-1 and -2 cloned DNAs contained an apparent deletion of about 30 base pairs in the restriction fragment containing the regulatory region (type alpha); 17% had a deletion of about 60 base pairs (type beta). The regulatory sequences were identical in all four clones representative of SVPML-1 and -2 type alpha grown in human and monkey cells. Thus the primary genomes of two isolates of SV40 from PML are identical in the region that is highly heterogeneous in JCV. The SVPML-alpha-DNAs have a net deletion of 30 base pairs and rearrangements within the transcriptional enhancer. The transcriptional promoter and origin of DNA replication is unaltered from that of SV40. Therefore the human neurotropism of SVPML appears to be a consequence of important rearrangements of SV40 sequences rather than acquisition of JCV-like sequences.