PAPILLOMA VIRUS ACTIONS ON HOST CELL GENE PRODUCTS

这项研究的主要目的是为了深入了解 乳头瘤病毒诱导的细胞转化现象，以及 通过关注变化，最终恶性转化 宿主细胞基因表达和其他对细胞基因的影响 与乳头瘤病毒（PV）表达相关的产品 基因. 这项工作首先全面审查了 在大约5000个宿主细胞基因产物的变化中， 描述了那些发生在细胞中的变化， 牛乳头瘤病毒1型（BPV-1），由棉尾兔 乳头瘤病毒（CRPV）及其克隆的PV DNA，包括 对一些被改造以改变 早期PV ORF的表达。 在本提案中，我们超越了最初的描述性 阶段的直接目标是收集更基本的 关于六种看似新的生物的性质和起源的信息 肽，似乎代表PV特异性诱导， BPV-1和CRPV转化的细胞蛋白质 细胞 我们还将探索一个新的假设， 从我们最初的研究来看，即病毒E2的产物 编码区（E2 ORF），已知其作为 在早期病毒基因表达中的反式激活因子， 也可作为反式激活因子， 基因. 这项研究将涉及使用E2表达载体， 进一步确定E2基因产物在肿瘤起源中的作用， 细胞蛋白质的PV特异性变化。 它将审查 回收的细胞mRNA的体外翻译产物， 确定在该水平是否发生感应。 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。 它将承担 将cDNA分子克隆至PV特异性细胞蛋白。 潜在的临床相关性包括最终开发 用于诊断和治疗的免疫试剂，以及 开发新的治疗方法，增强细胞对 病毒通过改变细胞因子或其他成分 在病毒的反式激活机制中起着关键作用- 宿主关系。

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.