Interaction of HIV with Macaque Genital Tract

描述（由申请人提供）：增加对男性对女性性传播机制的理解是本提案的长期目标，可用于促进杀菌剂和治疗HIV感染早期事件的治疗方法的开发。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靶点，但病毒如何在穿过上皮屏障后进入这些靶点细胞仍然是一个谜。为了深入了解这一过程，有人建议利用一种新技术来识别组织中HIV的单个病毒粒子。Hope实验室先前已经使用宫颈外和宫颈内组织外植体和生物工程上皮培养系统验证了该系统。然而，这些类型的系统只是试图模仿在体内发生的事情。现在是时候将这些研究扩展到雌性到雄性的性传播的动物模型上了。这些系统中最具特征的是恒河猴模型，使用SIV修饰使用HIV包膜蛋白（SHIV）。该提案寻求资助实验，以表征HIV与恒河猴雌性生殖道的相互作用，并提供HIV如何进入阴道粘膜中的靶细胞和那些首先被感染的细胞的见解。这些研究将确定女性生殖道中对艾滋病毒进入底层组织的屏障效率较低的部分。他们还将确定HIV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，这将为HIV如何进入组织并在组织内移动的机制提供见解。人类健康相关性：因此，这些拟议的研究与申请高度相关，因为更好地了解男性到女性的性传播机制可以用来促进开发杀微生物剂和治疗艾滋病毒感染早期事件（传播期事件）的疗法。

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).