Simian virus 40 regulatory region structural diversity and the association of viral archetypal regulatory regions with human brain tumors

The regulatory region (RR) of simian virus 40 (SV40) contains enhancer/promoter elements and an origin of DNA replication. Natural SV40 isolates from simian brain or kidney tissues typically have an archetypal RR arrangement with a single 72-basepair enhancer element. A rare simpler shorter SV40 RR exists that Jacks a duplicated sequence in the G/C-rich region and is termed protoarchetypal. Occasionally, SV40 strain variants arise de novo that have complex RRs, which typically contain sequence reiterations, rearrangements, and/or deletions. These variants replicate faster and to higher titers in tissue culture; we speculate that such faster-growing variants were selected when laboratory strains of SV40 were initially, recovered. SV40 strains with archetypal RRs have been found in some human brain tumors. The possible implications of these findings and a brief review of the SV40 RR structure are presented.