Trans-Acting Elements Encoded in Immediate Early Genes of DNA Tumor Viruses

Abstract

The adenovirus E1A region is capable of inducing the immortalization of primary rodent fibroblasts and cooperates with other genes such as adenovirus E1B, polyoma middle T or the ras gene to induce a fully transformed phenotype (see Land, this Vol., and Cuzin and Mougneau, this Vol.). It is probably the first transcription unit of adenovirus to be activated during lytic infection. Its gene products activate the transcription of other early regions of the viral genome. Several other early viral proteins produced in cells infected by DNA viruses also activate viral genes expressed during the later phases of the lytic cycle. Among these are the SV40 large T-antigen, the polyoma large T-antigen, the herpes virus immediate early (IE) proteins and the E2 gene-product of bovine papilloma virus (Spalholz et al. 1985). The tat proteins of the RNA containing human T-cell leukemia virus HTLV I and II also have a transactivating function (see Haseltine et al., this Vol.). All these genes have efficient promoters that are activated by cis-elements such as enhancers (see Schlokat and Gruss, this Vol.). The strong early viral promoters thus have a dual function: they are regulated by cis elements to ensure initiation of infection and their products trans-activate the promoter of other early viral genes to permit the virus to progress through its lytic cycle. Since most studies have been done with the adenovirus E1A region, I will review this gene as a model for the organization and the mechanism of action of trans-acting elements.