Control Elements for the Expression of DNA Tumor Viruses

Abstract

Expression of viral genes is essential for the multiplication of viruses. The early region of many members of the papova virus group encodes a multifunctional protein (T-Ag). One of the functions involves the initiation of DNA replication. DNA replication in turn seems to depend on a certain level of T-Ag. Thus, one important element possibly involved in host-range could be the viral promoter, controlling the expression of T-Ag. In addition to promoter elements, we and others recently described a control region on the viral genome which greatly increases the transcriptional activity of certain genes. This functional element was termed enhancer or activator. It differs from promoter elements in its ability to exert this function relatively independent of distance and orientation with respect to the coding region. The overall activity of the enhancer/activator is host-dependent, suggesting a possible involvement of host specific factors. In an effort to define critical nucleotides we have constructed and analyzed mutants containing multiple nucleotide exchanges within the SV40 72 bp repeat. Our results define nucleotides essential for the enhancer function. We furthermore determined the minimal activity of the A-gene required for a lytic cycle.