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Human papilloma virus type 16 (HPV-16) and herpes simplex virus type 2 (HSV-2) are human viruses implicated in the development of cancer, in particular cervical cancer. The ability of HSV-2 and HPV-16 to transform early passage human cells was examined in this report. For these studies, gingival fibroblasts were utilized. One gingival cell strain was derived from a normal individual (N-16). The second cell strain was derived from hyperplastic gingival tissue of an epileptic individual (R-30) treated with phenytoin, an antiseizure drug. A common side effect of phenytoin is the induction of gingival overgrowth. R-30 cells contained a stable chromosomal translocation between chromo-

Expression of herpes simplex virus 2 (HSV-2)-encoded ribonucleotide reductase (RR) is required for growth in nondividing cells. The functional enzyme is composed of a large and a small subunit. In virus-infected cells, RR is expressed temporally as a delayed early protein. However, the promoter regulatory region of the large subunit can function as an immediate early promoter in transient transfection assays, suggesting that expression may be quite complex. In this study, a 95-bp fragment derived from the open reading frame of the large subunit of RR (RR-A) functioned as a silencer when placed adjacent to a heterologous promoter. If the fragment was placed distal to the promoter, repression was relieved and in human keratinocytes promoter activity was consistently higher than control constructs. Exonuclease III protection assays revealed that nuclear factors from human keratinocytes as well as other primate cells specifically bind to this fragment. A 30-bp motif containing a consensus SP-1 binding site and an alternating Pu/Py element was protected in all cell lines. These results suggest that a 95-bp fragment in the open reading frame of HSV-2 RR-A plays a role in regulating viral gene expression.

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