TRANSFORMATION OF RODENT FIBROBLASTS BY ICP4, THE MAJOR TRANSACTIVATING PROTEIN OF HERPES-SIMPLEX VIRUS TYPE-1

Rat fibroblasts were transfected with a plasmid containing the IE3 gen e derived from the temperature sensitive HSV-1 mutant tsK. Three of fo ur clones expressing biologically active, temperature-sensitive ICP4, formed a substantial number of colonies in soft agar at the permissive temperature. During the first passages of cells, the transformed stat e of the major proportion of transformed cells was dependent on the co ntinuous activity of ICP4. In a smaller and distinct subpopulation of transformed cells, as well as after longer subcloning of cells, ICP4 w as no longer required for the maintenance of the transformed state, po inting to the induction of stable genomic changes by ICP4. Our data sh ow that ICP4 of HSV-1 is involved in transformation of fibroblasts. Tr ansformed cells are, however, subject to intracellular and intercellul ar control mechanisms.