Interferon-alpha elicits downregulation of human papillomavirus 18 mRNA in HeLa cells by selective repression of endogenous viral transcriptionJournal of interferon and cytokine research (1995)
We have reported that interferon-alpha inhibits HPV-18 mRNA in HeLa cells. Here we examine mechanisms by which IFN could modulate HPV expression. In northern blot experiments, we observed that interferon-alpha 2b treatment reduced HPV-18 mRNA levels in a time- and dose-dependent manner, with a maximal effect achieved at 48 h. Simultaneously, induction of 2-5A synthetase mRNA was verified as indicative of IFN action. The IFN regulatory effect on HPV-18 mRNA at 48 h required de novo protein synthesis. We performed run-on experiments to determine whether the IFN regulatory effect was at the transcriptional level. HPV-18 endogenous transcription was repressed using 200 and 1000 IU/ml. Interferon treatment did not affect HPV-18 mRNA stability, at least under our experimental conditions. To verify whether HPV-18 enhancer sequences were involved in the interferon effect, we transfected a construct containing the chloramphenicol acetyltransferase driven by the HPV-18 upstream regulatory region. The enzyme activity was unmodified on human keratinocytes and HeLa cells by interferon exposition. Our data demonstrate that interferon-alpha downregulates HPV-18 mRNA levels on HeLa cells by repressing nascent viral transcripts, possibly through regulatory cellular flanking regions.
Publication DateSummer June, 1995
Citation InformationSilvio E Perea, Omar Lopez-Ocejo, Rolando Garcia-Milian and Manuel De J Arana. "Interferon-alpha elicits downregulation of human papillomavirus 18 mRNA in HeLa cells by selective repression of endogenous viral transcription" Journal of interferon and cytokine research Vol. 15 Iss. 6 (1995) p. 495 - 501 ISSN: 1557-7465
Available at: http://works.bepress.com/rolando_garciamilian/15/