Epidermal growth factor induces, in the EL alpha 4-2 cell line, herpes simplex virus-1 alpha 4 gene transcription in the absence of the viral trans-activator VP16

We have constructed a fibroblast cell line (EL alpha 4-2) which constitutively expresses the alpha 4 gene of herpes simplex virus type 1. We studied the induction of the alpha 4 gene, in the absence of the viral activator VP16, by stimulating EL alpha 4-2 cells with different growth factors. Here we report that a rapid, transient induction of the alpha 4 gene occurs only when EL alpha 4-2 fibroblasts are stimulated with purified epidermal growth factor (EGF). Such an induction does not require de novo protein synthesis. The role of cellular factors on the EGF-mediated induction of the alpha 4 gene has been analyzed by gel mobility shift assays using nuclear extracts from EL alpha 4-2 cells stimulated or not with EGF. The results obtained show that two factors bind to TAATGARAT (R = purine) regardless of EGF-stimulation. We conclude that a mechanism, different from the one involving VP16, is responsible for alpha 4 gene activation in EL alpha 4-2 cells and that the DNA-protein architecture is maintained at the TAATGARAT regulatory site regardless of changes in the transcriptional state induced by EGF.