Modulation of HPV18 and BPV1 transcription in human keratinocytes by simian virus 40 large T antigen and adenovirus type 5 E1A antigen

Abstract

Transcription of early open reading frames initiated from the long control region (LCR) of HPV18 and BPV1 is known to be modulated by homologous and heterologous papillomarvirus E2 gene products. Using CAT constructs transfected into normal human keratinocytes, we show that SV40 large T antigen activates transcription from the LCR of both viruses, whereas Ad5-E1a antigen represses transcription from the HPV18-LCR but activates transcription from BPV1-LCR. Experiments using constructs containing subfragments of the HPV18-LCR cloned in enhancer configuration ahead of the SV40 early promoter or the HSV1-Tk promoter suggest that the effect of Ad5-E1a antigen on HPV18 transcription is probably due to a repression of the enhancer function of the LCR. The mechanism of transcription stimulation by SV40 large T antigen is less clear. The 230 bp Rsa1-Rsa1 central domain of the HPV18-LCR seems involved both in transcriptional stimulation by SV40 large T antigen and transcriptional inhibition by adenovirus E1a antigen.