IDENTIFICATION AND PRECLINICAL TESTING OF MICROBICIDES FOR HPV

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。该资助的R21阶段最近完成，筛选了450万个小分子的数据库，并确定了几种候选的HPV特异性杀微生物剂进行测试 我们现在将开始该提案的R33阶段，在非人灵长类动物模型中进行肛门生殖器HPV感染的研究，基于对雌性恒河猴生殖道中恒河猴乳头瘤病毒（RhPV 1）感染的监测。这一模式是最近在TNPRC通过一个试点项目开发的。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。 我们还开发了大量攻毒病毒，用于拟定的接种和检测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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anogenital Human Papillomaviruses (HPVs) are the most common sexually transmitted pathogen and the primary cause of cervical cancer. The R21 Phase of this grant was recently completed, screened a database of 4.5 million small molecules, and have identified several candidate HPV-specific microbicides for testing We now will begin the R33 phase of this proposal with studies in a nonhuman primate model for anogenital HPV infection, based upon monitoring infection by Rhesus papillomavirus (RhPV1) in the reproductive tract of female Rhesus macaques. This model 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. We have also developed a large stock of the challenge virus to be used for the proposed inoculations and testing of our candidate microbicide compounds for reduction or arrest of viremia and progression of RhPV1 anogenital papillomavirus infections in the nonhuman primate.