CONTROL OF PAPILLOMAVIRUS LATE TRANSCRIPTION

乳头状病毒晚期转录的控制

• 批准号: 3916849
• 负责人: C C BAKER
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916849
• 关键词: Papillomavirus; acetyl coA acetyltransferase; cell differentiation; cell growth regulation; cell transformation; chloramphenicol; cis trans isomerization; complementary DNA; cow; cutaneous papilloma; disease /disorder model; endonuclease; epithelium; fibroma; gene expression; genetic manipulation; genetic mapping; genetic models; genetic promoter element; genetic regulation; genetic transcription; horses; keratinocyte; messenger RNA; molecular cloning; molecular genetics; neoplastic cell culture for noncancer research; nucleic acid sequence; transfection; transposon /insertion element; viral carcinogenesis; virus genetics; virus replication

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.

乳头状瘤病毒引起良性和恶性病变， 高等脊椎动物的鳞状上皮。 完全溶解 这些病毒的周期（包括晚期基因表达）只发生在 在鳞状上皮的分化细胞中。 恶性 培养物中的病变和感染细胞不产生病毒。 一个 了解乳头状瘤的转录调控 病毒及其与上皮细胞调控的关系 分化是必要的阐明的作用， 乳头状瘤病毒在癌发生中的作用 我们用牛 乳头瘤病毒1型（BPV-1）作为研究 后期转录及其调控。 BPV-1转录 生产性感染的组织已经被映射的组合， cDNA克隆、核酸酶S1保护和引物延伸， 与BPV-1纤维瘤组织和BPV-1- 转化的C127细胞。 一种强病毒转录启动子 （称为晚期启动子）已被确定，这是积极的，只有 在生产性感染的上皮中。 所有其他病毒启动子都是 在纤维乳头状瘤和BPV-1转化的细胞中都有活性。 我们目前正试图确定顺式和反式作用 参与控制晚期启动子的元件 并确定这些反式作用因子可能 在上皮细胞分化中起作用。 后期控制 转录也是通过顺式作用元件介导的。 晚期区域。 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 已经确定了一个因素， 当置于多聚腺苷酸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其作用机制。 病毒和/或细胞因子与这些因子反式相互作用， 还将确定要素。