CHLAMYDIA TRACHOMATIS + SHIV: CO-INFECTION MODEL DEVELOPMENT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在人类中，现在人们普遍认为，其他性传播感染的存在极大地促进了性伴侣之间艾滋病毒的传播和感染。例如，衣原体引起的宫颈内感染引起下生殖道炎症，这可能使感染性病毒颗粒更有效地交换，从而增强艾滋病毒感染。利用这种增强病毒摄取的潜在机制，我们计划用衣原体感染“初始化”猴子，然后尝试用SHIV粘膜攻击感染它们。我们打算在长尾猕猴中建立一种共感染模型，在该模型中，在先前感染沙眼衣原体的动物中，单次粘膜攻击后可实现可重复的SHIV感染率（80-100%）。在成功开发这种联合感染模型后，我们期望将其用于局部杀微生物剂产品的有效性测试，以预防艾滋病毒感染。为了评估局部杀菌剂产品防止病毒摄取的能力，我们将衣原体感染的动物暴露于局部杀菌剂产品中，然后用SHIV攻击。这样的临床前试验将极大地帮助筛选产品进入临床研究的过程。

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. In humans, it is now widely believed that the presence of other sexually transmitted infections greatly facilitate the transmission and acquisition of HIV between sexual partners. As an example, chlamydia induced endocervical infection causes inflammation of the lower reproductive tract, which may allow for more efficient exchange of infectious viral particles, thereby enhancing HIV infection. Using this potential mechanism for enhanced viral uptake, we plan to 'prime' monkeys with a chlamydial infection, then attempt to infect them by mucosal challenge with SHIV. We intend to develop a co-infection model in the pig-tailed macaque, in which a reproducible SHIV infection rate (80-100%) is achieved after a single mucosal challenge in animals previously infected with Chlamydia trachomatis. Upon successful development of this co-infection model, we expect to use it for efficacy-testing of topical microbicide products, in preventing SHIV infection. To evaluate the ability of a topical microbicide product to prevent viral uptake, we will expose chlamydia infected animals to a topical microbicide product, then challenge with SHIV. Such pre-clinical testing will greatly aid in the process of screening products for enrollment in clinical studies.