CONTROL OF PAPILLOMAVIRUS LATE TRANSCRIPTION

乳头瘤病毒可引起良性和恶性病变 高等脊椎动物的鳞状上皮。完整的歌词 这些病毒的周期(包括晚期基因表达)仅发生在 在鳞状上皮的分化细胞中。恶性 培养中的病变和受感染的细胞不会产生病毒。一个 对乳头状瘤转录调控的理解- 病毒及其与上皮细胞调控的关系 辨证对于阐明细胞因子的作用是必要的 乳头瘤病毒在癌症发生中的作用我们用的是牛 人乳头瘤病毒1型(BPV-1)作为研究人乳头瘤病毒 晚期转录及其调控。BPV-1转录于 高效感染的组织已经通过组合绘制了 C DNA克隆、核酸酶S1保护、引物延伸和 与对BPV-1纤维瘤组织和BPV-1的类似分析相比- 转化C127细胞。一种强大的病毒转录启动子 (称为后期启动者)已确定仅处于活动状态 在产生性感染的上皮中。所有其他病毒启动子都是 在纤维乳头状瘤和BPV-1转化的细胞中均有活性。 我们目前正试图确定顺式和反式作用 参与后期启动子控制的因素 并确定这些反式作用因子可能起的作用 在上皮细胞分化中发挥作用。对后期的控制 转录也是通过顺式作用元件在 晚期地区。这些元素很可能通过 转录终止、多聚腺苷酸化和/或mRNA 不稳定。已经确定了一种元素，它降低了 当被放置在多聚腺苷化位点上游时的基因表达 在真核表达载体中。附加顺式作用元件 正在绘制地图，并确定它们的行动机制。 病毒和/或细胞因子以反式方式与这些 还将确定元素。

The papillomaviruses cause benign and malignant lesions of squamous epithelia in higher vertebrates. The complete lytic cycle of these viruses (including late gene expression) occurs only in the differentiated cells of the squamous epithelium. Malignant lesions and infected cells in culture do not produce virus. An understanding of the transcriptional regulation of the papilloma- viruses and its relationship to the control of epithelial cell differentiation is necessary for the elucidation of the role of the papillomaviruses in carcinogenesis. We have used bovine papillomavirus type 1 (BPV-1) as a model system for the study of late transcription and its control. BPV-1 transcription in productively infected tissue has been mapped by a combination of cDNA cloning, nuclease S1 protection, and primer extension and compared to similar analyses for BPV-1 fibroma tissue and BPV-1- transformed C127 cells. A strong viral transcriptional promoter (called the late promoter) has been identified which is active only in productively infected epithelium. All other viral promoters are active in both the fibropapilloma and in BPV-1-transformed cells. We are currently attempting to identify the cis- and trans-acting elements which are involved in the control of the late promoter and to determine the role which these trans-acting factors may play in epithelial cell differentiation. Control of late transcription is also mediated through cis-acting elements in the late region. These elements most likely function through transcription termination, polyadenylation, and/or mRNA destabilization. One element has been identified which decreases gene expression when placed upstream of the polyadenylation site in a eukaryotic expression vector. Additional cis-acting element are being mapped and their mechanisms of action determined. Viral and/or cellular factors which interact in trans with these elements will also be identified.