Interferon-alpha elicits downregulation of human papillomavirus 18 mRNA in HeLa cells by selective repression of endogenous viral transcription

J Interferon Cytokine Res. 1995 Jun;15(6):495-501. doi: 10.1089/jir.1995.15.495.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • Down-Regulation / drug effects
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Enzymologic / drug effects
  • HeLa Cells
  • Humans
  • Interferon-alpha / pharmacology*
  • Papillomaviridae / genetics*
  • RNA, Messenger / biosynthesis*
  • RNA, Viral / biosynthesis*
  • Repressor Proteins / pharmacology*
  • Transcription, Genetic / drug effects*


  • Interferon-alpha
  • RNA, Messenger
  • RNA, Viral
  • Repressor Proteins
  • 2',5'-Oligoadenylate Synthetase