Detection of authentic SV40 DNA sequences in human brain and bone tumours

This report summarizes our follow-up studies of SV40 DNA sequences in human brain tumors of early childhood and our confirmation of the presence of SV40 DNA in human osteosarcomas. We examined brain tumors and osteosarcoma samples by the polymerase chain reaction (PCR) using primers from four separated regions of the SV40 genome. Sequence analysis confirmed that authentic SV40 DNA was present. The regulatory region of each tumor-associated viral DNA was of archetypal length (non-duplicated enhancer); sequence variation was noted at the extreme C-terminus of the large T-antigen (T-ag) genes. Infectious SV40 was recovered from one brain tumor. We sequenced the entire early genomic region from three human isolates of SV40 and two laboratory strains originally recovered from monkeys. The predicted amino acid sequence of the large T-ags showed remarkable sequence conservation among isolates, except for a small variable region identified at the C-terminus of the protein. There were no human-isolate-specific changes detected that could serve to distinguish a human variant of SV40 nor were any tumor-type-specific viral markers observed. Based on these data, we conclude that authentic SV40 is associated with some human brain and bone tumors and that multiple SV40 strains can infect humans.