Strand Orientation of SV40 Transcription in Cells infected by Non-defective Adenovirus 2-SV40 Hybrid Viruses

Abstract

CELLS productively infected with the double-stranded DNA tumour virus SV40 synthesise viral RNA in two phases. Before viral DNA replication begins, only early genes are transcribed (early RNA); after the onset of viral DNA replication, both early and late gene sequences are transcribed (early-plus-late RNA)^{1, 2}. Using the technique of hydroxyapatite (HA) chromatography to separate the strands of SV40 DNA^3–5, or an RNA-RNA hybridisation method⁶, it has been shown that the early template occupies about one third of one strand (the (−) strand), while the late template occupies about two thirds of the opposite strand (the (+) strand). In cells transformed by 5V40, most or all of the early template is transcribed, and additional regions of the (−) strand may be transcribed as well^{5, 7}; however, little if any transcription occurs from the (+) strand⁷. Furthermore, the synthesis of SV40 T antigen in SV40-transformed cells is totally resistant to interferon⁸. These observations suggest that, in the transformed cell, SV40 gene expression is under the control of the host rather than the viral genome. This apparent alteration in control may be the result of the integration of SV40 DNA into chromosomal DNA⁹.