Epidermal growth factor induces, in the ELα4-2 cell line, herpes simplex virus-1 α4 gene transcription in the absence of the viral trans-activator VP16

We have constructed a fibroblast cell line (ELα4-2) which constitutively expresses the α4 gene of herpes simplex virus type 1. We studied the induction of the α4 gene, in the absence of the viral activator VP16, by stimulating ELα4-2 cells with different growth factors. Here we report that a rapid, transient induction of the α4 gene occurs only when ELα4-2 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 α4 gene has been analyzed by gel mobility shift assays using nuclear extracts from ELα4-2 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 α4 gene activation in ELα4-2 cells and that the DNA-protein architecture is maintained at the TAATGARAT regulatory site regardless of changes in the transcriptional state induced by EGF. © 1991.