ANTIGENIC VARIABILITY AMONG HPVS INVOLVED IN GENITAL CAN

人乳头瘤病毒(HPV)是一个极其多样化的大家族。 专门感染人类上皮细胞的病毒病原体。一定的 人乳头瘤病毒的类型与肺癌有关 肛门生殖道，最显著的是子宫鳞状细胞癌 宫颈。在美国，宫颈癌发病率为 在美洲原住民和西班牙裔妇女中尤其高。在大学里学习 新墨西哥大学的研究表明，子宫颈癌在 这些人群最常与HPV16型有关，但 大约30%的病例与HPV18型、31型和33型有关。 目前全世界都在努力调查HPV- 相关癌症可以通过使用HPV疫苗或 人乳头瘤病毒蛋白作为免疫调节剂修饰的可能性 已确定的HPV感染的自然病史。人类乳头瘤病毒的研究是 受阻于缺乏体外系统来支持 病毒的传播。因此，很可能会努力 开发HPV疫苗将重点使用HPV编码的重组 用作免疫原的蛋白质。然而，目前还不知道是否不同 给定HPV类型的分离株在抗原性上相同或抗原性相同 变种。如果不同的HPV16分离株具有抗原性变异， 例如，然后用编码的重组蛋白进行免疫 原型毒株可能无法预防其他HPV16的感染 菌株。我们已经证明了自然产生的人类的存在 识别HPV衣壳蛋白和主要HPV的抗体 转化蛋白质。这些蛋白质可能是疫苗的候选者。 发展。我们建议使用聚合酶链式反应(PCR) 从HPVDNA中扩增这些蛋白的编码序列的技术 存在于生殖道样本中。这些编码序列将被表达 作为细菌重组蛋白，并将用作抗原靶标 免疫印迹分析。人乳头瘤病毒重组蛋白来源于 临床菌株将被测试与人类抗体的反应性 已知与原型编码的重组蛋白发生反应 HPV型的菌株。通过这种方式，我们将能够确定 临床分离株在抗原性上与原型相似。

The human papillomaviruses (HPVs) are a large and extremely diverse family of viral pathogens that exclusively infect human epithelial cells. Certain types of human papillomaviruses are associated with carcinomas of the anogenital tract, most notably squamous cell carcinomas of the uterine cervix. In the United States, cervical carcinoma incidence rates are particularly high among Native American and Hispanic women. Studies at the University of New Mexico have demonstrated that cervical carcinomas in these populations are most commonly associated with HPV type 16, but that approximately 30% of cases are associated with HPV types 18, 31 and 33. Worldwide efforts are now underway to investigate the possibility that HPV- associated cancers could be prevented by the use of HPV vaccines, or the possibility that HPV proteins could be used as immune modulators to modify the natural history of established HPV infections. The study of HPVs is hindered by the lack of an in vitro system that will support the propagation of the viruses. It is likely, therefore, that efforts to develop HPV vaccines will focus on the use of HPV-encoded recombinant proteins for use as immunogens. However, it is not known whether different isolates of a given HPV type are antigenically identical or antigenically variant. If different isolates of HPV 16 were antigenically variant, for example, then immunization with recombinant proteins encoded by the prototype strain may not protect against infections with other HPV 16 strains. We have demonstrated the presence of naturally-occurring human antibodies that recognize HPV capsid proteins and the major HPV transforming protein. These proteins are likely candidates for vaccine development. We propose to use the polymerase chain reaction (PCR) technique to amplify the coding sequences for these proteins from HPV DNAs present in genital tract samples. These coding sequences will be expressed as bacterial recombinant proteins and will be used as antigen targets in Western immunoblot assays. The HPV recombinant proteins derived from the clinical strains will be tested for reactivity with human antibodies that are known to react with recombinant proteins encoded by the prototype strain of that HPV type. In this way, we will be able to determine whether the clinical isolates are antigenically similar to the prototypes.