Effect of gamma-interferon or cycloheximide treatment on viral and c-myc transcripts in bovine-papillomavirus-type-1-transformed primary mouse fibroblasts

Abstract

We have studied the effect of gamma-interferon (IFN-gamma) treatment on the transcription of viral and c-myc oncogenes in bovine papillomavirus type 1 (BPV-1)-transformed mouse fibroblast cell lines. Upon IFN-gamma treatment, viral transcripts always decreased in cell lines containing episomal BPV-1 DNA, while the effect was variable in cell lines containing integrated BPV-1 DNA. Two series of tumour cell lines established by in vivo passage of B6B71 (episomal) and B6B31-J (integrated) cells via nude mice (NuTu A) into immunocompetent C57BL/6 mice (NuTuA B6Tul) also showed a decrease and an increase, respectively, in viral transcripts upon IFN-gamma treatment. IFN-gamma also reduced c-myc transcription in all cell lines derived from tumours, but increased it in the transformed cell cultures. There was selection of c-myc oncogene transcripts in all the tumour-derived cell lines as compared to their transformed cell cultures. Cycloheximide treatment increased both viral and c-myc gene transcripts 3- to 20-fold in all cell lines. These results imply that IFN-gamma produced locally by immunological mechanisms may influence the expression of Papillomavirus oncogenes, and the response to IFN-gamma treatment may change when the viral DNA is integrated into the host genome.