Definition of a region required for transformation in E1a of adenovirus 12

In order to define functionally important regions of the E1 a gene of adenovirus 12 (Ad12), a number of Ad12 mutants were studied. These mutants share an identical 69-bp deletion in the first exon of E1a as well as duplications of a long terminal repeat sequence at the end of the Ad12 genome. The mutants are fully competent for replication and growth in their normal hosts and have a host range extended to include the Vero cell line of African green monkey origin. The partially deleted E1a can stimulate the expression of all early adenoviral genes as well as the cellular heat shock gene, the transcription of which is stimulated by Ad5 E1a. However, plasmids containing the deleted E1a plus wild type E1b were unable to effect a transformation of either primary rat embryo fibroblasts or on an established cell line following transfection. Further, the mutant viruses were defective in generating tumors in newborn hamsters. We conclude that the deleted sequence of E1a described here is critical for transformation by E1a but is not necessary for multiplication of the virus or the transcriptional activating function of the gene.