Interaction of HIV with Macaque Genital Tract

HIV 与猕猴生殖道的相互作用

• 批准号: 7993524
• 负责人: Ann M Carias
• 金额: $ 2.87万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993524
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Affect; Animal Model; Biomedical Engineering; CD4 Positive T Lymphocytes; Cells; Cervical; Data; Development; Epithelial; Epithelial Cells; Epithelium; Event; Female; Funding; Genital system; Goals; HIV; HIV vaccine; Health; Human; Individual; Infection; Label; Laboratories; Langerhans cell; Life; Macaca; Macaca mulatta; Modeling; Mucous Membrane; Play; Process; Request for Applications; Role; SIV; Sexual Transmission; Simple Columnar Epithelium; Stratified Squamous Epithelium; System; T-Lymphocyte; Time; Tissues; Vagina; Viral; Virion; Virus; Virus Diseases; Woman; comparative; env Gene Products; in vivo; insight; macrophage; male; microbicide; new technology; novel; pandemic disease; simian human immunodeficiency virus; therapeutic development; therapy design; transmission process; virus envelope

DESCRIPTION (provided by applicant): An increase in the understanding of the mechanisms of male-to-female sexual transmission is the long-term goal of this proposal which can be used to facilitate the development of microbicides and therapies designed to treat the early events of HIV infection. Although mucosal T cells and Langerhans cells have been identified as potential early targets of infection in the female genital tract how the virus gains access to these target cells after traversing the epithelial barriers remains a mystery. To gain insights into this process it is being proposed to utilize a new technology that allows the identification of individual virions of HIV in tissue. The Hope Lab has previously validated this system using ectocervical and endocervical tissue explants and bioengineered epithelial culture systems. However, these types of systems only attempt to mimic what takes place in vivo. It is now time to extend these studies to an animal model for female-to-male sexual transmission. The most characterized of these systems is the rhesus macaque model using SIV modified to use the HIV envelope protein (SHIV). The proposal seeks to fund experimentation to characterize the interaction of HIV with the rhesus macaque female genital tract and provide insights into how HIV gains access to target cells in the vaginal mucosa and those cells first infected. These studies will identify portions of the female genital tract that are less efficient as barriers to HIV entering the underlying tissue. They will also identify the potential interaction of HIV with target cells in the vaginal mucosa and possibly give insight into what cells are infected primarily. They may also identify the interaction of HIV with cellular compartments that will provide insights into the mechanisms of how HIV can enter and move within the tissue. HUMAN HEALTH RELEVANCE: Therefore, these proposed studies are highly relevant to the request for applications because a better understanding of the mechanisms of male-to-female sexual transmission can be used facilitate the development of microbicides and therapies designed to treat the early events of HIV infection (peritransmission events).

描述（由申请人提供）：增加对男性到女性性传播机制的了解是该提案的长期目标，可用于促进杀微生物剂和旨在治疗艾滋病毒感染早期事件的疗法的开发。尽管粘膜T细胞和朗格汉斯细胞已被确定为女性生殖道感染的潜在早期目标，但病毒在穿过上皮屏障后如何进入这些目标细胞仍然是个谜。为了深入了解这一过程，有人提议利用一项新技术来识别组织中的 HIV 病毒颗粒。希望实验室此前已使用宫颈外和宫颈内组织外植体以及生物工程上皮培养系统验证了该系统。然而，这些类型的系统仅试图模仿体内发生的情况。现在是时候将这些研究扩展到女性到男性性传播的动物模型了。这些系统中最具特色的是使用 SIV 进行修改以使用 HIV 包膜蛋白 (SHIV) 的恒河猴模型。该提案旨在资助实验，以表征艾滋病毒与恒河猴雌性生殖道的相互作用，并深入了解艾滋病毒如何接触阴道粘膜中的目标细胞和首先感染的细胞。这些研究将确定女性生殖道中阻碍艾滋病毒进入底层组织效率较低的部分。他们还将确定艾滋病毒与阴道粘膜靶细胞的潜在相互作用，并可能深入了解哪些细胞主要受到感染。他们还可能确定 HIV 与细胞区室的相互作用，从而深入了解 HIV 如何进入组织并在组织内移动的机制。人类健康相关性：因此，这些拟议的研究与申请请求高度相关，因为更好地了解男性向女性性传播的机制可以促进杀微生物剂和旨在治疗艾滋病毒感染早期事件（围传播事件）的疗法的开发。