Transcriptional regulation of human papillomavirus type 16 LCR by different C/EBP beta isoforms

During genital human papillomavirus (HPV) infection several cytokines are r eleased, such as interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alp ha), IL-6, and IL-8. These cytokines may play a role in the immune surveill ance against viral infection. Two of these cytokines, IL-1 and TNF alpha, s uppress the transcription of the HPV16 early genes. CAATT/ enhancer binding protein beta (C/EBP beta), which is activated by IL-1 and TNF alpha, has b een suggested to act as a mediator of this transcriptional downregulation. C/EBP beta contains three different translation initiation sites that can l ead probably by leaky ribosome scanning to the generation of three isoforms of C/EBP beta, namely full-length C/EBP beta, liver enriched transcription al activator protein (LAP), and liver enriched inhibitory protein (LIP). Wh en transiently expressed in C33A and HeLa cells, the first two C/EBP beta i soforms'activate the HPV16 long control region (LCR). LIP, which acts as an antagonist of C/EBP beta, represses the HPV16 LCR activity. Our observatio n that treatment of HeLa cells with IL-1 leads to induction of LIP supports the hypothesis that the LCR downregulation by IL-1 is mediated by LIP. Mel . Carcinog. 28:42-50, 2000. (C) 2000 Wiley-Liss, Inc.