Regulation of Viral Transcription and DNA Replication by the SV40 Large T Antigen

Abstract

Simian Virus 40 (SV40) provides a particularly useful model for studying gene regulation at the molecular level because it is one of the simplest and most thoroughly characterized (Tooze 1980) viral systems known to undergo a well-defined developmental cycle in mammalian cells. The entire nucleotide sequence of the 5243 base pair genome of SV40 has been determined (Reddy et al. 1978; Fiers et al. 1978) and important regions such as the origin of replication, transcriptional promoters, structural gene boundaries, splice junctions, and positions of mutations have been located. The small double-stranded circular genome of SV40 encodes only five or six genes and consequently relies in large part on the host cell machinery to carry out complex regulated processes such as transcription and replication. During lytic infection of monkey cells, SV40 undergoes a temporal pro-gram of gene expression that is controlled in part by viral coded proteins (Tegtmeyer1972; Cowan et al. 1973; Tegtmeyer et al. 1975; Reed et al. 1976). Immediately after infection, the SV40 A and F genes, encoding the large T (Black et al. 1963; Tegtmeyer1975) and small t (Prives et al. 1978; Crawford et al. 1978; Sleigh et al. 1978) antigens respectively, are expressed. Transcription of these early viral genes by the host RNA polymerase II originates from a region of the genome located at approximately 0.67–0.70 fractional units on the conventional genome map (Fig. 1) (Sambrook et al. 1973; Khoury et al. 1973; Jackson and Sugden 1972; Khoury et al. 1975). During this early phase of the lytic cycle, SV40 DNA replication does not occur (Tegtmeyer 1912) and expression of the structural capsid proteins is detectable only at very low levels (Cowan et al. 1973; Alwine et al. 1977).