Rat fibroblasts were transfected with a plasmid containing the IE3 gene derived from the temperature sensitive HSV-1 mutant tsK. Three of four 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 state of the major proportion of transformed cells was dependent on the continuous activity of ICP4. In a smaller and distinct subpopulation of transformed cells, as well as after longer subcloning of cells, ICP4 was no longer required for the maintenance of the transformed state, pointing to the induction of stable genomic changes by ICP4. Our data show that ICP4 of HSV-1 is involved in transformation of fibroblasts. Transformed cells are, however, subject to intracellular and intercellular control mechanisms.

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