IDENTIFICATION AND PRECLINICAL TESTING OF MICROBICIDES FOR HPV

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心赠款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 人类乳头状瘤病毒（HPV）是最常见的性传播病原体，也是宫颈癌的主要原因。最近，TNPRC通过试点项目开发了一种使用恒河猴乳头瘤病毒（RhPV 1）的PV感染非人模型。我们能够确认5只恒河猴中有5只感染了HPV，并有进展为癌前病变的迹象。该资助的R21阶段筛选了450万个小分子的数据库，并确定了几种候选HPV特异性杀微生物剂进行测试。 为了开始本提案的R33阶段，在非人灵长类动物模型中进行肛门生殖器HPV感染研究，我们对25只雌性恒河猴进行了血清学和分子筛选，以评估既往暴露于RhPV 1的情况，并确定了12只血清阴性雌性，将继续进行研究。我们还开发了大量攻毒病毒，用于拟定的接种，并等待测试我们的候选杀微生物剂化合物，以减少或阻止非人灵长类动物中RhPV 1肛门生殖器乳头状瘤病毒感染的病毒血症和进展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Anogenital Human Papillomaviruses (HPVs) are the most common sexually transmitted pathogen and the primary cause of cervical cancer. A nonhuman model of PV infection using Rhesus papillomavirus (RhPV1) was recently developed at TNPRC through a pilot project. We were able to confirm infection of 5 of 5 rhesus with indications of progression to precancerous lesions, typical of HPV. The R21 Phase of this grant screened a database of 4.5 million small molecules, and have identified several candidate HPV-specific microbicides for testing. To begin the R33 phase of this proposal with studies in a nonhuman primate model for anogenital HPV infection, we conducted both serological and molecular screening of 25 female Rhesus macaques to assess prior exposure to RhPV1 and have identified 12 seronegative females that will go forward for the study. We have also developed a large stock of the challenge virus to be used for the proposed inoculations and await testing of our candidate microbicide compounds for reduction or arrest of viremia and progression of RhPV1 anogenital papillomavirus infections in the nonhuman primate.