Functional Studies of Soluble Innate Host Factors in HIV and Bacteria

为了更好地了解艾滋病毒感染期间口腔的独特性以及随后的 治疗，本项目将定义HIV，特异性可溶性宿主 防御分子和口腔细菌。根据从项目1（改建）获得的数据， 项目2（HIV和HAART对口腔微生物多样性的影响 和定植，以及项目3（HIV对胃肠道中可溶性介质和微生物的影响）， 该项目的重点是唾液中的抗菌和抗病毒活性。讨论的问题 包括（1）从口腔对艾滋病毒的反应中可以学到什么， 用于其他粘膜部位？(2)宿主的防御分子和细胞因子是如何在 艾滋病毒感染和后续治疗？(3)抗病毒和抗菌活性如何变化 在艾滋病毒感染期间，和（4）在口腔、肠道和胃肠道中的HIV-1变体的比较， 血液可能受局部宿主因素的影响。最终，我们希望了解为什么直肠 艾滋病毒的传播比口头传播更有效，这些信息如何传播？ 可以用来降低艾滋病感染率。为了实现这些目标，我们 提出了以下具体目标： 具体目标1。为了定量已知与宿主细胞相互作用的可溶性先天宿主因子的子集， 艾滋病病毒和细菌 具体目标2。为了定量来自HIV-， HIV+和HIV+/HAART受试者以及单个纯化蛋白 并确定口腔和直肠组织是否在它们的易感性方面存在差异， 体外HIV感染。 具体目标3。为了描述艾滋病毒储存库的遗传和表型特征， 口腔、血液和胃肠道。

To better understand the uniqueness of the oral cavity during HIV infection and subsequent therapy, this project will define the functional relationships among HIV, specific soluble host defense molecules and oral bacteria. Building on the data obtained from Projects 1 (Alteration is the salivary proteome in HIV), Project 2 (Effect of HIV and HAART on oral microbial diversity and colonization, and Project 3 (Effect of HIV on soluble mediators and microbes in the Gl tract), this project focuses on antibacterial and antiviral activities in saliva. Questions to be addressed include (1) what can be learned from how the oral cavity responds to HIV that could be useful for other mucosal sites?, (2) how host defense molecules and cytokines are modulated during HIV infection and subsequent therapy?, (3) how antiviral and antibacterial activities change during HIV infection?, and (4) a comparison of the HIV-1 variants in the oral cavity, gut, and blood that may be influenced by local host factors. Ultimately we hope to understand why rectal transmission of HIV is much more efficient than oral transmission and how this information could be used to decrease the rate of HIV infection. In order to accomplish these goals we have proposed the following Specific Aims: Specific Aim 1. To quantitate a subset of soluble innate host factors that are known to interact with both HIV and bacteria Specific Aim 2. To quantitate the anti-HIV and antibacterial activity of samples from HIV-, HIV+, and HIV+/HAART subjects as well as from individual purified proteins and to determine whether oral and rectal tissues differ in their susceptibility to HIV infection in vitro. Specific Aim 3. To characterize genetic and phenotypic features of the HIV reservoir in the oral cavity, blood, and gastrointestinal tract.