The Role of Cis- and Trans-Acting Functions in Simian Virus 40 Gene Regulation

Abstract

Simian virus 40 (SV40) is a small DNA tumor virus, the circular genome [5243 base pairs (bp)] of which encodes at least two early proteins and four late gene products (Tooze, 1980). The lytic cycle of this virus is expressed over a temporal course in permissive African green monkey kidney cells. Early viral gene expression is predominant in the first 10-12 hr postinfection. The early viral program appears to be represented by a single transcription unit that gives rise to one primary messenger RNA (mRNA). This transcript is then differentially spliced into one of two mRNAs that encode the two early SV40 proteins, large tumor (large-T) and small tumor (small-t) antigens. All subsequent events in the lytic cycle appear to depend on the presence of a functional large-T antigen, which, through binding to three large-T-antigen-binding sites near the origin for DNA replication: (1) modulates downward the level of early gene transcription through a repressorlike function, (2) stimulates the initiation of viral DNA replication, and (3) both directly and indirectly activates the SV40 late transcriptional program (see Fig. 1). A set of late mRNA molecules Open image in new window Figure 1 Genomic map and control region of SV40. The diagram presents the control region for expression of the SV40 early genes (large-T and small-t antigens) and late genes (VP1, 2, and 3). The origin for viral DNA replication (or) is flanked by the early transcriptional control sequences, including the Goldberg-Hogness box (AT), the three 21-bp repeats (each containing two copies of a GC-rich hexanucleotide), and the tandem 72-bp enhancer element. The early transcripts are initiated predominantly at position E early in infection and shift to position L after DNA replication. The late viral transcripts have heterogeneous 5′ ends, indicated by dots. Reprinted from Hamer and Khoury (1983) with permission. encodes the structural proteins of SV40, namely, VP1, VP2, and VP3. In addition, a 61-amino-acid polypeptide, the agnoprotein, is made late in the lytic cycle. While the function of this protein is not entirely clear, it appears to play a role in encapsidation or assembly of the mature viral particles. Furthermore, the late agnoprotein may play a role in regulation of late gene expression.