Remm M, Brain R, Jenkins J R
Estonian Biocenter, Tartu.
Nucleic Acids Res. 1992 Nov 25;20(22):6015-21. doi: 10.1093/nar/20.22.6015.
Human papillomaviruses (HPV-s) have been shown to possess transforming and immortalizing activity for many different, mainly keratinocyte cell lines and they have been detected in 90% of anogenital cancer tissues, which suggests a causative role in the induction of anogenital and other tumours. We have exploited a quantitative assay to identify and characterize the origin of replication of the human papillomavirus type 18 (HPV-18), one of the most prevalent types in the high-risk HPV group. Replication of HPV origin fragments was studied transiently by cotransfection with a protein expression vector providing replication proteins E1 and E2. We have localized the HPV-18 origin to nucleotides 7767-119. This region contains three E2 binding sites and an essential A/T rich DNA region (nucleotides 9-35) that is partly homologous to the E1 binding site found in bovine papillomavirus type 1 (BPV-1) genome. At least one of the three E2 binding sites was absolutely required for origin function; addition of other E2 sites had cooperative stimulating effect. This is the first quantitative analysis of the E2 binding sites for papillomavirus replication.
人乳头瘤病毒（HPV）已被证明对许多不同的主要是角质形成细胞系具有转化和永生化活性，并且在90%的肛门生殖器癌组织中被检测到，这表明其在肛门生殖器及其他肿瘤的诱发中起致病作用。我们利用一种定量分析方法来鉴定和表征人乳头瘤病毒18型（HPV-18）的复制起点，HPV-18是高危HPV组中最常见的类型之一。通过与提供复制蛋白E1和E2的蛋白质表达载体共转染，对HPV起点片段的复制进行了瞬时研究。我们已将HPV-18起点定位到核苷酸7767 - 119。该区域包含三个E2结合位点和一个必需的富含A/T的DNA区域（核苷酸9 - 35），该区域与牛乳头瘤病毒1型（BPV-1）基因组中发现的E1结合位点部分同源。三个E2结合位点中至少有一个对于起点功能是绝对必需的；添加其他E2位点具有协同刺激作用。这是对乳头瘤病毒复制的E2结合位点的首次定量分析。
