Cloning of the herpes simplex virus ICP4 Gene in an adenovirus vector: Effects on adenovirus gene expression and replication

To assess the ability of the herpes simplex virus ICP4 protein to complement adenovirus E1a mutants we have constructed an adenovirus type 5 vector containing a temperature-sensitive ICP4 gene, under control of its own promoter, within the E1 region of the genome. The recombinant virus expresses ICP4 in cells which are permissive (293) or nonpermissive (KB and R970-5) for viral replication, and at levels which approximate those obtained in herpes simplex infection. The adenovirus-encoded protein is functional in that it complements an ICP4 deletion mutant of herpes simplex virus; however, it is incapable of complementing adenovirus E1a mutants for viral growth or DNA replication. At the level of activation of gene expression, ICP4 stimulates the expression of the adenovirus E2a gene but not that of other early genes. Our results indicate that ICP4 does not possess all of the functions of the E1a proteins and, furthermore, that adenovirus early genes differ in their susceptibility to heterologous trans-activators.