ROLE OF PAPILLOMAVIRUS IN CERVICAL NEOPLASIA

最近的分子病毒学和免疫学研究表明， 人乳头瘤病毒感染与宫颈非典型增生的关系 子宫颈。这些观察结果的重要性得到了强调。 因为不典型增生被认为是宫颈的前驱病变 癌症。这项提案的具体目标是描述HPV的特征 通过分子克隆从异型增生中分离出序列 使用以下方法确定与这些病变相关的各种HPV类型 定向抗体的分子杂交和免疫学试验 抗病毒类型特异性多肽或寡肽。 将人乳头瘤病毒序列克隆到载体或载体上， 随后以与已知HPV类型的DNA杂交为特征。 这些克隆的DNA将用于斑点转移和原位杂交 对不典型增生和宫颈癌的实验。序列分析 病毒DNA将为合成 细菌表达载体中的病毒类型特异性结构多肽 通过固相化学合成寡肽的体系或方法。这个 产生的抗体将被用来筛选活组织标本以确定 与退行性不典型增生相关的HPV类型 进展到更严重的疾病。针对目标的抗体 乳头瘤病毒属特有的非结构(转化)蛋白将是 用于宫颈免疫细胞化学研究的细菌合成 癌症。 从宫颈发育不良(退行性或进行性)的行为来看 将具有预后和/或诊断价值 宫颈HPV感染的转归。这样的信息可以提供一个 更合理地处理宫颈肿瘤。

Recent molecular virologic and immunologic studies have shown a relationship between human papillomavairus (HPV) infection and dysplasia of the uterine cervix. The significance of these observations is underscored by the fact that dysplasias are considered precursor lesions to cervical carcinoma. The specific aims of this proposal are to characterize HPV sequences from dysplasias by molecular cloning for the purpose of identifying the various HPV types associated with these lesions using molecular hybridization and immunological tests with antibodies directed against virus type-specific poly- or oligopeptides. HPV sequences will be cloned into plasmid or Charon vectors and subsequently characterized by hybridization to DNAs of known HPV types. These cloned DNAs will be used in blot transfer and in situ hybridization experiments with dysplasias and cervical carcinomas. Sequence analysis of the viral DNAs will provide necessary information for the synthesis of virus type-specific structural polypeptides in bacterial expression vector systems or synthesis of oligopeptides by solid-phase chemistry. The resultant antibodies will be used to screen biopsy specimens to determine the HPV type associated with dysplasias which regress and those which progress to more serious disease. Antibodies directed against papillomavirus genus-specific nonstructural (transforming) proteins will be synthesized in bacteria for use in immunocytochemical studies on cervical cancers. From the behavior of cervical dysplasia (regression or progression) it would be of prognostic and/or diagnostic value to be able to predict the outcome of HPV infection of the cervix. Such information could provide a more rational approach to the management of cervical neoplasia.