Struyk L, van der Meijden E, Minnaar R, Fontaine V, Meijer I, ter Schegget J
Department of Virology, Academic Medical Center, University of Amsterdam, The Netherlands.
Mol Carcinog. 2000 May;28(1):42-50.
During genital human papillomavirus (HPV) infection several cytokines are released, such as interleukin-1 (IL-1), tumor necrosis factoralpha (TNFalpha), IL-6, and IL-8. These cytokines may play a role in the immune surveillance against viral infection. Two of these cytokines, IL-1 and TNFalpha, suppress the transcription of the HPV16 early genes. CAATT/ enhancer binding protein, (C/EBPbeta), which is activated by IL-1 and TNFalpha, has been suggested to act as a mediator of this transcriptional downregulation. C/EBPbeta contains three different translation initiation sites that can lead probably by leaky ribosome scanning to the generation of three isoforms of C/EBPbeta, namely full-length C/EBPbeta, liver enriched transcriptional activator protein (LAP), and liver enriched inhibitory protein (LIP). When transiently expressed in C33A and HeLa cells, the first two C/EBPbeta isoforms activate the HPV16 long control region (LCR). LIP, which acts as an antagonist of C/EBPbeta, represses the HPV16 LCR activity. Our observation 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.
在生殖器人乳头瘤病毒（HPV）感染期间，会释放多种细胞因子，如白细胞介素-1（IL-1）、肿瘤坏死因子α（TNFα）、IL-6和IL-8。这些细胞因子可能在针对病毒感染的免疫监视中发挥作用。其中两种细胞因子，IL-1和TNFα，可抑制HPV16早期基因的转录。CAATT/增强子结合蛋白（C/EBPβ）可被IL-1和TNFα激活，有人认为它是这种转录下调的介导因子。C/EBPβ包含三个不同的翻译起始位点，可能通过核糖体渗漏扫描导致产生三种C/EBPβ异构体，即全长C/EBPβ、肝脏富集转录激活蛋白（LAP）和肝脏富集抑制蛋白（LIP）。当在C33A和HeLa细胞中瞬时表达时，前两种C/EBPβ异构体可激活HPV16长控制区（LCR）。作为C/EBPβ拮抗剂的LIP可抑制HPV16 LCR活性。我们观察到用IL-1处理HeLa细胞会导致LIP的诱导，这支持了IL-1介导LCR下调是由LIP介导的这一假说。
