PAPILLOMAVIRUS MODEL SYSTEM FOR MICROBICIDE TESTING

人乳头瘤病毒（HPV）代表了一些最常见的 性传播疾病超过70种HPV类型已被 已确定，某些类型已被强烈暗示为病因 宫颈癌、阴道癌、阴茎癌和皮肤癌的发病因素。 杀微生物剂作为抗乳头瘤病毒剂尚未被描述。 最近，已经建立了几种体外乳头瘤病毒感染模型。 记录，使筛选杀微生物剂成为可能， 抗乳头瘤病毒活性。 我们的长期目标是建立三种乳头状瘤病毒的有效性， 用于测试抗乳头瘤病毒制剂的体外感染性模型。的 我们建议使用的模型是（i）BPV-1诱导的小鼠病灶形成 C127细胞，（ii）兔细胞系Sf 1 Ep和RK-13的瞬时感染 CRPV感染，和（iii）在CRPV之前用HPV-11感染人包皮芯片。 移植到无胸腺小鼠的肾包膜中。我们确定 中和性单克隆抗体（N-MAbs）可以作为有效的抗- 在这三个模型系统中的每一个中的乳头瘤病毒试剂，因此 提供已知针对这些病毒的唯一阳性对照抗病毒剂。 N-MAbs显示，在所有三种体外系统中， 病毒结合和内化的动力学，这表明所有三个 模型描述了传染性的共同机制。我们将联合收割机 在体外试验系统中用新的人 将感染HPV-11的阴道异种移植模型（描述于 项目1，项目负责人John Kreider博士），以确认有效性 抗乳头状瘤病毒制剂。

Human papillomaviruses (HPVs) represent some of the most common of the sexually transmitted diseases. More than 70 HPV types have been identified, and some types have been strongly implicated as causative agents in the onset of cervical, vaginal, penile and skin cancers. Microbicides as anti-papillomavirus agents have not been described. Recently, several in vitro papillomavirus infectivity models have been documented that make feasible the screening of microbicides for potential anti-papillomavirus activity. Our long term goal is to establish the validity of three papillomavirus in vitro infectivity models for testing anti-papillomavirus formulations. The models we propose to use are (i) BPV-1 induced focus-formation of mouse C127 cells, (ii) transient infection of rabbit cell lines Sf1Ep and RK-13 with CRPV, and (iii) infection of human foreskin chips with HPV-11 prior to grafting into the renal capsule of athymic mice. We have established that neutralizing monoclonal antibodies (N-MAbs) can operate as effective anti- papillomavirus reagents in each of these three model systems, and thus provide the only positive control anti-virucide known for these viruses. The N-MAbs showed that in all three in vitro systems there were similar kinetics of virus binding and internalization, suggesting that all three models describe a common mechanism of infectivity. We will combine the results of screening in the in vitro assay systems with a novel human vaginal xenograft model that will be infected with HPV-11 (described in Project #1, Dr. John Kreider, Project leader) to confirm the effectiveness of anti-papillomavirus formulations.