Interferon-β treatment of cervical keratinocytes naturally infected with human papillomavirus 16 episomes promotes rapid reduction in episome numbers and emergence of latent integrants

摘要: Following integration of human papillomavirus (HPV) into the host genome, overexpression viral oncogenes E6 and E7 requires loss transcriptional repressor functions E2. A key step in HPV-related carcinogenesis is therefore clearance residual episomes, which encode As spontaneous HPV-16 episomes vitro associated with increased expression antiviral genes inducible by type I interferon (IFN), we used W12 model to examine effects exogenous IFN-beta on cervical keratinocytes containing as a result 'natural' infection vivo. In contrast studies cells transfected HPV-31 or bovine papillomavirus, caused rapid reduction numbers episomes. This was emergence bearing previously latent integrants, there E7. Our data indicate that integrated can exist minority mixed population without exerting selective advantage until episome are reduced. The kinetics cell death changes transcription translation observed support where integrants initially present also generalized resulting integrant de-repression. We conclude hasten transition from episomal naturally infected keratinocytes. Greater emphasis should be placed models carcinogenesis. provide strongest evidence date treating lesions inducing an IFN response may cause clinical progression.