PAPILLOMA VIRUS ACTIONS ON HOST CELL GENE PRODUCTS

乳头状瘤病毒对宿主细胞基因产物的作用

• 批准号: 3191408
• 负责人: DONALD A YOUNG
• 金额: $ 18.3万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3191408
• 关键词: Papillomavirus; chickens; complementary DNA; gene expression; genetic manipulation; genetic translation; messenger RNA; molecular cloning; nucleic acid hybridization; nucleic acid probes; oncoproteins; rabbit papillomavirus; temperature sensitive mutant; transposon /insertion element; viral carcinogenesis; virus DNA; virus genetics

The broad of this research are to gain now insights into the phenomena of papillomavirus-induced cell transformation, and ultimately malignant conversion, by focusing on the changes in host-cell gene expression and other influences on cell gene products that are linked to the expression of papillomavirus (PV) genes. This work began with a comprehensive examination of changes in about 5000 host-cell gene products in which we described those changes that occurred in cells transformed by the bovine papillomavirus type 1 (BPV-1), by the cottontail rabbit papillomavirus (CRPV) and their cloned PV DNAs, including the responses to a number constructs engineered to alter the expression of early PV ORFs. In this proposal we are proceeding beyond the initial descriptive stage with the immediate aim of gathering more fundamental information about the nature and origins of six seemingly new peptides that appear to represent PV-specific inductions in cellular proteins that appear in BPV-1 and CRPV transformed cells. We will also be exploring a new hypothesis that evolved from our initial studies, namely, that the products of the viral E2 coding region (E2 ORF), which are known to serve as transactivators in the expression of the early viral genes, may also serve as transactivators altering the expression of cellular genes. The research will involve the use of E2 expression vectors to further establish the role of E2 gene products in the origins of the PV-specific changes in cellular proteins. It will examine the products of in vitro translation of recovered cellular mRNAs to determine whether the inductions occur at the level. It will utilize specific antibodies to detect changes in E2 proteins and develop and utilize coding-region specific hybridization probes to detect expression of E2 mRNAs. And it will undertake the molecular cloning of cDNAs to the PV-specific cellular proteins. Potential clinical relevance includes the eventual development of immunoreagents for diagnostic and therapeutic use, and the development of new therapies that enhance cellular resistance to viruses by altering cellular factors or other components involved in transactivating mechanisms that play critical roles in virus- host relationships.

这项研究的主要目的是深入了解 乳头瘤病毒诱导的细胞转化现象，以及 最终恶性转化，通过关注 宿主细胞基因表达和对细胞基因的其他影响 与乳头瘤病毒 (PV) 表达相关的产品 基因。 这项工作从全面检查开始 大约 5000 个宿主细胞基因产物发生了变化，其中我们 描述了经转化的细胞中发生的那些变化 1 型牛乳头瘤病毒 (BPV-1)，由棉尾兔传播 乳头瘤病毒 (CRPV) 及其克隆的 PV DNA，包括 对一些旨在改变的结构的反应 早期 PV ORF 的表达。 在本提案中，我们将超越最初的描述性 阶段的直接目标是收集更多基本信息 有关六种看似新事物的性质和起源的信息 似乎代表 PV 特异性诱导的肽 BPV-1 和 CRPV 转化中出现的细胞蛋白 细胞。 我们还将探索一个新的假设 根据我们的初步研究，即病毒 E2 的产物 编码区（E2 ORF），已知作为 早期病毒基因表达中的反式激活因子可能 也可作为反式激活剂改变细胞的表达 基因。 该研究将涉及使用 E2 表达载体 进一步确定E2基因产物在物种起源中的作用 细胞蛋白质的 PV 特异性变化。 它将检查 回收的细胞 mRNA 体外翻译产物 确定感应是否发生在该水平。 它将 利用特异性抗体检测 E2 蛋白的变化 开发和利用编码区特异性杂交探针 检测E2 mRNA的表达。 并且它将承担 将 cDNA 分子克隆到 PV 特异性细胞蛋白。 潜在的临床相关性包括最终的发展 用于诊断和治疗用途的免疫试剂，以及 开发增强细胞抵抗力的新疗法 通过改变细胞因子或其他相关成分来消灭病毒 反式激活机制在病毒中发挥关键作用 宿主关系。