Functional Analyses of Human Adenovirus Types 5 and 12 Chimeric Early Region 1A Recombinants

Human adenoviruses have the ability to transform rodent cells in vitro. They are classified into several subgroups based on their tumorigenicity in vivo and DNA sequence homology. Thus, the adenoviruses offer a valuable system with which transforming ability and tumorigenic potential can be analysed comparatively between oncogenic and non-oncogenic serotypes in terms of molecular genetics and molecular biology.In order to analyse the transforming E1A genes of human adenoviruses, we constructed four chimeric E1A genes between non-oncogenic type 5 and highly oncogenic type 12 using restriction sites. They are i） type NI composed of type 12 first exon and type 5 second exon of the E1A genes, ii） type C with type 5 first exon and type 12 second exon, iii） type N carrying the N-terminal half of type 12 first exon and the rest from type 5 sequence, and iv） type NC composed of type N first exon and type 12 second exon. By analyses of transcriptional regulatory activity and transforming activity of these chimeric E1A genes, the following results were obtained. 1） All the chimeric E1A genes exhibited transcriptional activation, showing the E1A sequences of Ad 5 and Ad 12 are interconvertible. 2） Type NI showed the strongest transcriptional activation among the four chimeric E1A genes.3） Only type C showed weak transcriptional repression.4） Types NI and C, but not types N or NC, showed the transforming ability on the established rat cell line 3Y1. 5） Primary baby rat kidney cells were transformed only by type C chimeric E1A gene. 6） The above results suggest the presence of interaction between intramolecular subregions of the E1A gene product.departmental bulletin pape