COMPARISON OF REGULATORY SEQUENCES AND ENHANCER ACTIVITIES OF SV40 VARIANTS ISOLATED FROM PATIENTS WITH NEUROLOGICAL DISEASES

The genomic regulatory regions of human isolates of SV40 were compared by nucleotide sequencing and by biological assays of their transcriptional enhancers. SVAST is a defective genome and SVMEN an infectious genome molecularly cloned from human astrocytoma and meningioma, respectively (Krieg and Scherer, 1984). SVPML is an isolate from a case of progressive multifocal leukoencephalopathy (Weiner et al., 1972). SVAST contains a duplication of the regulatory region. One copy is virtually identical to that of SV40; the other bears a deletion of the minimal enhancer and is associated with an insertion of early/late sequences derived from the terminus of replication. The latter copy, together with its insertion, is inserted at nucleotide 4966 (SV40 number). SVMEN has an almost exact deletion of one of the 72-base-pair repeats of the natural SV40 enhancer. The regulatory sequences of SVPML were reported earlier (Martin, 1989). The enhancer activity in CV-1 cells of the lytic virus, SVPML, is 36% that of SV40. In contrast, the SVAST and SVMEN enhancers are more effective, being equal to or 64% that of SV40, respectively. The possibility that SVPML and SVAST/SVMEN originated from different variants of SV40 is discussed.