Interaction of HIV with Macaque Genital Tract

HIV 与猕猴生殖道的相互作用

• 批准号: 8197331
• 负责人: Ann M Carias
• 金额: $ 2.92万
• 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/8197331
• 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）：对男性到女性性传播机制的理解增加是该提案的长期目标，可用于促进旨在治疗HIV感染早期事件的菌心和疗法的发展。尽管粘膜T细胞和Langerhans细胞已被鉴定为女性生殖道中潜在的感染靶标的潜在的早期感染靶标，该病毒在穿越上皮屏障后如何获得对这些靶细胞的访问仍然是一个谜。为了洞悉这一过程，正在提议利用一种允许识别组织中艾滋病毒病毒体的新技术。 Hope Lab先前已经使用宫颈和宫颈组织外植体和生物工程上皮培养系统验证了该系统。但是，这些类型的系统仅尝试模仿体内发生的事情。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。这些系统最有特征的是使用SIV修饰的恒河猕猴模型使用HIV包膜蛋白（SHIV）。该提案旨在资助实验，以表征HIV与猕猴的女性生殖道的相互作用，并提供有关艾滋病毒如何获得阴道粘膜中靶细胞和那些首先感染的细胞中靶细胞访问的见解。这些研究将确定一部分女性生殖道作为进入潜在组织的HIV障碍的效率较低。他们还将确定HIV与阴道粘膜中靶细胞的潜在相互作用，并可能深入了解主要感染哪些细胞。他们还可以鉴定HIV与细胞室的相互作用，这些室将提供有关HIV如何进入组织内和移动的机制的见解。人类健康相关性：因此，这些提出的研究与应用要求高度相关，因为可以更好地了解男性到女性性传播的机制，可以促进旨在治疗HIV感染早期事件（递种事件）的菌心和疗法的发展。