PAPILLOMAVIRUS MODEL SYSTEM FOR MICROBICIDE TESTING

用于杀菌剂测试的乳头状病毒模型系统

• 批准号: 6235309
• 负责人: NEIL D CHRISTENSEN
• 金额: $ 11.86万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235309
• 关键词: SCID mouse; Treponema pallidum; antiviral agents; athymic mouse; bovine papillomavirus; clone cells; disease /disorder model; disease /disorder proneness /risk; drug screening /evaluation; human papillomavirus; human tissue; model design /development; neutralizing antibody; nonhuman therapy evaluation; pathologic process; rabbit papillomavirus; vagina; xenotransplantation

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.

人乳头瘤病毒(HPV)代表了一些最常见的 性传播疾病。目前已有70多种HPV类型 已确定，并且一些类型被强烈地牵连为原因 导致宫颈癌、阴道癌、阴茎癌和皮肤癌的药物。 杀微生物剂作为抗乳头瘤病毒的药物还没有被描述。 最近，几种体外乳头瘤病毒感染性模型已经被 文件证明，使筛选潜在的杀微生物剂成为可能 抗乳头瘤病毒活性。 我们的长期目标是确定三种乳头瘤病毒在 用于测试抗乳头状瘤病毒制剂的体外感染性模型。这个 我们建议使用的模型是：(I)BPV-1诱导的小鼠焦点形成 C127细胞，(II)兔细胞系Sf1Ep和RK-13的瞬时感染 感染CRPV；及(Iii)感染HPV-11之前的人包皮切片 无菌小鼠肾被膜内移植。我们已经确定 中和性单抗(N-MAb)可作为有效的抗 乳头瘤病毒试剂在这三个模型系统中的每一个中，因此 为这些病毒提供唯一的阳性对照抗病毒药物。 N-单抗表明，在所有三个体外系统中， 病毒结合和内化的动力学，表明这三种病毒 模型描述了一种常见的传染性机制。我们将结合 一种新人类在体外检测系统中的筛选结果 将感染HPV-11的阴道异种移植模型(见 项目#1，项目负责人John Kreider博士)以确认有效性 抗乳头瘤病毒制剂。