The effects of interferon (IFN)-α, IFN-β and IFN-γ on human papillomavirus (HPV) oncogene expression were studied in various cervical carcinoma cell lines containing integrated copies of either HPV type 16 or HPV type 18. The levels of E6 and E7 transcripts were examined 6 h and 30 h after treatment with IFN. In HeLa cells, all three classes of IFNs effected a decrease in the level of HPV-18 E6 and E7 transcripts. On the other hand, none of the IFNs altered the level of these transcripts in C-4II cells. Only IFN-γ decreased the level of HPV-16 E6 and E7 transcripts in CaSki and HPK1A cells, while IFN-γ actually increased the level of these transcripts in SiHa cells. This differential IFN regulation of HPV expression in various cervical cancer cell lines may account for the contradictory clinical results observed after treatment of cervical cancer with IFN.
Northern blot and RT-PCR analyses indicated that the human papillomavirus E4 open reading frame is expressed in HeLa cells. Because integration at the E1 or E2 open reading frame would place the viral upstream regulatory region downstream of the viral late genes, the expression of E4 in HeLa cells is most likely regulated by host cellular promoter(s) or unidentified viral promoter(s) in the E2 region. Primer extension analysis and transient transfection experiments with luciferase reporter constructs under the transcriptional control of various subgenomic fragments of HPV-18 were carried out to identify and characterize functional promoters within the E2 region. The in vivo activity of a novel promoter located within the 5'-end region of the E2 open reading frame of human papillomavirus type 18 is demonstrated.
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