Adenovirus type 5 and adenovirus type 12 recombinant viruses containing heterologous E1 Genes are viable, transform rat cells, but are not tumorigenic in rats

Abstract

Two sets of adenovirus type 5 (Ad5)-adenovirus type 12 (Ad12) recombinant viruses were constructed and analyzed. In one case the Ad12 E1A, E1B, or E1A plus E1B genes were substituted for the corresponding Ad5 genes in the Ad5 chromosome. The second set contained the Ad5 E1A, E1B, or E1A plus E1B genes in place of the cognate Ad12 genes in the Ad12 chromosome. The hybrid viruses were all viable and expressed the appropriate E1 antigens. They were able to transform secondary rat fibroblasts, but at reduced efficiency as compared to either parental virus. Fibroblasts transformed with the recombinant Ad5 virus carrying the Ad12 E1A plus E1B genes were tumorigenic in newborn, syngeneic rats. Some of the cell lines transformed with the Ad5 virus containing the Ad12 E1A gene were tumorigenic but none of the recombinants with the Ad12 E1B gene was able to induce tumors in this assay. Although Ad12 was tumorigenic, none of the Ad5 or Ad12 recombinant viruses induced tumors in newborn rats injected either intracerebrally or subcutaneously with virus particles.