The effect of E1 mutations on biochemical transformation by an adenovirus carrying the herpes simplex virus thymidine kinase gene in region E3.

A series of human adenovirus type 5 (Ad5) vectors has been constructed in which a vector containing the human herpes simplex virus thymidine kinase (TK) gene has been recombined with several Ad5 early region 1 (E1) mutants. The resulting viruses were used to study host-virus interactions in TK- rat cells and to examine the importance of E1 functions in a biochemical transformation assay. One of the most important parameters affecting transformation efficiency in this system was the cytotoxicity of the transforming virus. Ad5 viruses expressing the E1a 289 amino acid protein were all highly cytotoxic and induced significantly fewer colonies than did less cytotoxic mutants which were defective in expression of the 289 amino acid product. When correction was made for differential cell viability the variation in transformation efficiencies was considerably reduced although some E1a mutants still demonstrated an enhanced ability to transform in comparison to wt virus. The significance of these results to morphological transformation by adenoviruses is discussed.