Specific induction of cellular gene transcription in herpes simplex virus type 2-transformed cells

In spite of much work, the mechanism of oncogenic transformation by herpes simplex virus (HSV) is as yet unknown. It has been proposed that HSV type 2 (HSV-2) can transform cells by a 'hit and run' mechanism. In the past we have demonstrated that several polypeptides can be immunoprecipitated from HSV-2-transformed cells, but not from control cells or adenovirus-transformed cells, by rabbit hyperimmune sera to HSV-2. It is possible that the expression of these proteins might be the result of activation of cellular genes during transformation. We have now isolated cDNAs representing transcripts of genes that are expressed at higher levels in HSV-2-transformed hamster embryo fibroblasts than in the parental cells. Cytoplasmic transcripts and genomic sequences homologous to three clones (pAA8, pHD1 and pLC7) were analysed. Northern blot analyses showed that 0.75 kb transcripts which hybridize to the three cDNAs were present in HSV-2-transformed cells and were completely absent or present at low levels in control hamster fibroblasts. These transcripts were not present in mouse cells transformed by other DNA viruses or by a chemical carcinogen. The expression of these transcripts seemed to be confined to certain HSV-2-transformed cell lines. Southern blot analysis suggested that the 0.75 kb transcripts corresponding to these cDNAs may have arisen from a single gene. Nuclear run-off experiments indicated that activation occurred at the level of transcription. The activation of the gene or genes corresponding to these cDNAs may be an integral part of the mechanism of transformation by HSV-2.