Organization and expression of oncogenic human adenovirus transforming genes

The transforming genes of the oncogenic human adenoviruses (Ad) reside within the left 7-8% of the viral genome. The organization and the expression of the entire Ad12 E1 region (the leftmost 11.2%) including the transforming genes, 3,860 nucleotide pairs, have been analyzed. Nucleotide sequencing and mRNA mapping studies on the entire E1 region made it possible to assign sites of mRNA initiations, splicings and terminations, and the regions coding for polypeptides at the nucleotide level. Amino acid sequences of the highly-oncogenic Ad12 E1 polypeptides thus predicted were compared with those of non-oncogenic Ad5, and the existence of a high degree of homologies in most of the Ad E1 polypeptides was shown between highly-oncogenic Ad12 and non-oncogenic Ad5. Among the viral-specific mRNAs identified, not only species corresponding to those synthesized in infected KB cells during early stages of productive infection, but also unique chimeric ones containing sequences of viral-viral or cellular-viral junctions were detected in cells transformed by Ad12 and Ad7 transforming genes. Some cDNA clones of the chimeric mRNA species as well as genomic DNA clones of the junction regions from Ad7 transformed cells were isolated and analyzed.