THE EFFECTS OF ALCOHOL ON SIV PATHOGENESIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 很明显，艾滋病毒感染和饮酒之间存在关联。然而，确定酒精摄入是否会导致增加感染风险或易感性的生理或免疫状况，而不是简单地导致人们从事更危险的行为，这在人类身上是很难破译的。我们继续在控制良好的猕猴模型中检查SIV和酒精使用的相互作用，这可以区分这些因素。今年，我们开始了一系列基于肠道通透性和细胞增殖的新研究，以确定酒精是否加速了SIV感染和疾病进展的发病机制。我们正在测量饮酒对肠道和/或细菌副产物释放到体循环的影响，这是否会增加全身或局部炎症，以及这些因素是否会增加肠道和外周淋巴组织中T细胞的破坏或周转速度。我们已经指定并启动了8只雄性猕猴，目前正在测试它们在饮酒时对SIV感染的粘膜和系统免疫反应。在另一个系列中，我们正在研究对女性生殖道的同样影响，看看酒精是否会增加阴道内的炎症和/或这是否会增加艾滋病毒的阴道传播率。到目前为止，已有四只雌性动物被指派进行这些研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is clearly an association between HIV infection and alcohol use. However, determining whether alcohol intake results in physiologic or immunologic conditions that increase the risk or susceptibility to infection rather than simply resulting in persons engaging in riskier behavior simply cannot be easily deciphered in humans. We are continuing to examine the interaction SIV and alcohol use in the well-controlled macaque model, which can distinguish these factors. This year we began a new series of studies based on intestinal permeability and cell proliferation to determine whether alcohol accelerates the pathogenesis of infection and disease progression with SIV. We are measuring the effects of alcohol use on release of intestinal and/or bacterial byproducts into the systemic circulation, whether this increases systemic or local inflammation, and whether these factors increase the rates of T cell destruction or turnover in intestinal and peripheral lymphoid tissues. We have assigned and started 8 male macaques and are currently testing their mucosal and systemic immune responses to SIV infection while on alcohol. In another series we are looking at the same effects on the female reproductive tract to see if alcohol increases inflammation in the vagina and/or whether this could increase the rate of vaginal HIV transmission. Four female animals have been assigned to date for these studies.