Simian virus 40 T antigen binds to host cell chromosomes

Abstract

T ANTIGEN of simian virus 40 (SV40) is the product of the A gene of the virus1 and has been shown to have a role in the establishment and maintenance of transformation2–5. T antigen has also been shown to be required for the initiation of each round of viral DNA synthesis6 and for induction of host DNA synthesis7–11. Furthermore, it has been suggested that T antigen may initiate DNA synthesis in transformed cells and thereby help maintain those cells in the transformed state6,12–14. The SV40 genome has three preferential binding sites for T antigen, one of which is at or near the site at which viral DNA synthesis is initiated15. The binding of T antigen to eukaryote DNA is less well defined but shows a preference for double-stranded over single-stranded DNA16. Similar findings have been reported for tumour-specific transplantation antigen17. SV40 nucleohistone has also been reported to bind T antigen in amounts threefold greater than does native SV40 DNA18. To investigate the role of T antigen in the regulation of the host cell, we have asked whether host chromosomes bind detectable amounts of T antigen; and, if so, whether the binding is restricted to specific chromosomes or to specific chromosomal loci. Although earlier studies have suggested that T antigen is associated with nuclear chromatin of infected cells19, this study is the first to report the binding of SV40 T antigen to mammalian chromosomes.