VAGINAL TRANSMISSION OF A PATHOGENIC RT-SHIVTC IN CYNOMOLGUS MACAQUES

食蟹猴中致病性 RT-SHIVTC 的阴道传播

• 批准号: 8172794
• 负责人: Che-Chung Tsai
• 金额: $ 23.26万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172794
• 关键词: Antibodies; Autopsy; Budgets; Cells; Computer Retrieval of Information on Scientific Projects Database; Dose; Exocervix; Funding; Grant; HIV; HIV-1; Immune response; Infection; Institution; Irrigation; Macaca; Macaca fascicularis; Measures; Modeling; Mucous Membrane; Nature; Population; Rectum; Research; Research Personnel; Resources; Route; Serum; Sexual Transmission; Small Intestines; Source; Surface; United States National Institutes of Health; Vagina; Viral Proteins; Virus; Virus Diseases; base; chemokine; chemotherapy; cytokine; efficacy evaluation; ileum; jejunum; lymph nodes; microbicide; mucosal site; non-nucleoside reverse transcriptase inhibitors; peripheral blood; rectal; response; simian human immunodeficiency virus; transmission process; vaginal transmission; viral DNA; viral RNA

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. The objective of this project is to develop a validated macaque model for sexual transmission of HIV by intravaginal (ivag) and intrarectal (ir) routes using a well-characterized RT-SHIV containing the RT of HIV-1. The rationale and significance of this project are described in the "Background and Significance" section. Considering the budget restriction, this project will focus on an ivag transmission of RT-SHIV in cynomolgus macaques (Macaca fascicularis). We will determine the virus-dose response to systemic infectivity after ivag exposure. The primary parameters of infection will include viral RNA, viral DNA and infectious cells in peripheral blood and the mucosa of the ectocervix, vagina, rectum and gut. We will characterize the nature of systemic and local infection of RT-SHIV in peripheral blood and mucosal surfaces of vagina, ectocervix, and rectum (by periodic lavage) and small intestines (at necropsy) and surrounding lymph nodes. These secondary parameters of infection are to identify the infected cell population and accessory factors (i.e. cytokines and chemokines which facilitate virus infection) at different mucosal sites: ectocervix, vagina, rectum and small intestine (jejunum and ileum). Additional secondary parameters of infection are to compare mucosal and systemic immune responses to RT- SHIV; so we will measure titers of SIV-antibodies in vaginal and rectal secretions and in serum obtained from peripheral blood, and detect specific antibodies to viral proteins produced in mucosa and/or serum. In summary, the objective of this study is ultimately to develop the successful RT-SHIV infection model in the cynomolgus macaque by vaginal transmission. Moreover, this established RT-SHIV macaque model will be useful for the efficacy evaluations of not only NNRTI-based microbicide candidates but also NNRTI and NRTI for systemic chemotherapy.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的目的是使用包含含有HIV-1 RT的良好特征的RT-SHIV来开发经过验证的猕猴对HIV的性传播，以通过直肠内（IVAG）和直肠内（IR）路线进行性传播。该项目的理由和意义在“背景和意义”部分中描述了。考虑到预算限制，该项目将集中于Cynomolgus Macaques（Macaca fascicularis）中RT-SHIV的IVAG传播。我们将确定IVAG暴露后对全身感染性的病毒剂量反应。感染的主要参数包括外周血中的病毒RNA，病毒DNA和传染性细胞以及骨膜，阴道，直肠和肠道的粘膜。我们将表征RT-SHIV的全身感染和局部感染在阴道，骨膜内膜和直肠（通过周期性灌洗）和小肠（在尸检时）和周围淋巴结的小肠（通过周期性灌洗）和小肠（通过周期性灌洗）和小肠（通过周期性的灌洗）和周围淋巴结的性质。这些感染的这些次要参数是在不同的粘膜部位确定感染的细胞群和辅助因子（即促进病毒感染的细胞因子和趋化因子）：Ectocervix，ecticervix，dagina，直肠和小肠（jejunum和ileum）。感染的其他次要参数是比较粘膜和全身免疫反应对RT-SHIV；因此，我们将测量阴道和直肠分泌中SIV抗体的滴度以及从外周血获得的血清中，并检测粘膜和/或血清中产生的病毒蛋白的特定抗体。总而言之，这项研究的目的最终是通过阴道传播在cynomolgus猕猴中开发成功的RT-SHIV感染模型。此外，这种已建立的RT-SHIV猕猴模型将不仅可用于对基于NNRTI的基于NNRTI的杀微生物候选者的功效评估，而且还可以用于全身化学疗法的NNRTI和NRTI。