PAPILLOMAVIRUS DNA AND ANTIGENS 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乳腺癌异型增生的关系 子宫颈 强调了这些意见的重要性 由于发育不良被认为是宫颈癌的先兆病变， carcinoma. 该提案的具体目标是描述HPV的特征， 通过分子克隆从发育不良获得的序列， 确定与这些病变相关的各种HPV类型， 分子杂交和免疫学试验， 针对病毒类型特异性多肽或寡肽。 HPV序列将被克隆到质粒或Charon载体中， 随后通过与已知HPV类型的DNA杂交来表征。 这些克隆的DNA将用于印迹转移和原位杂交 发育不良和宫颈癌的实验。 序列分析 病毒DNA将为合成 细菌表达载体中的病毒型特异性结构多肽 系统或通过固相化学合成寡肽。 的 产生的抗体将用于筛选活检标本，以确定 与退化的发育不良相关的HPV类型和 发展为更严重的疾病。 针对以下的抗体 乳头瘤病毒属特异性非结构（转化）蛋白将被 用于宫颈癌免疫细胞化学研究 癌的 从宫颈发育不良的行为（退化或进展）， 将具有预后和/或诊断价值，能够预测 宫颈HPV感染的后果 这些信息可以提供一个 更合理的方法来管理宫颈肿瘤。

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.