ALCOHOL, SIV INFECTION AND HOST DEFENSE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。酗酒和人类免疫缺陷病毒（HIV）感染是常见的，并经常在同一个人共存。长期以来，人们都知道饮酒会抑制先天免疫和特异性免疫的关键方面，从而增加宿主对感染的易感性。HIV感染主要对表达CD 4膜受体的免疫细胞发挥其致病作用，这导致CD 4+细胞的进行性耗竭、免疫监视受损、机会性感染和死亡。目前，关于这两种免疫抑制状态如何相互作用以改变针对原发性病毒感染和/或继发性机会性感染的宿主防御机制的信息很少。该项目的重点是确定酒精对恒河猴SIV感染的进展和后遗症的影响，因为它与原发感染本身和继发感染的发展有关。我们的假设是，酒精作为辅助因子加速SIV感染的进展，以及增加宿主对机会性感染的易感性，这反过来又会进一步加速SIV感染的进展。本研究通过解决3个具体目的来验证这一假设：1）确定饮酒对SIV原发感染、SIV感染进展以及随后机会性感染发展的影响。2)在体内研究饮酒和SIV感染对肺先天免疫系统的单独和联合作用。3)确定饮酒对实验性肺内感染引起的SIV疾病进展指数的体内影响。在一个明确定义和公认的非人灵长类HIV感染模型的背景下解决这些具体目标，将提供关于酒精对改变宿主对HIV原发感染及其进展的防御作用的新的和重要的信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcohol abuse and human immunodeficiency virus (HIV) infection are common and frequently coexist in the same individual. Alcohol consumption has long been known to suppress critical aspects of both innate and specific immunity thereby increasing host susceptibility to infections. HIV infection primarily exerts its pathogenic effects on immune cells expressing CD4 membrane receptor which leads to progressive depletion of the CD4+cells, compromised immunosurveillance, opportunistic infections, and death. Currently, there is little information on how these two immunosuppressive states interact to alter host defense mechanisms directed against both the primary viral infection and/or secondary opportunistic infections. The focus of this project is to determine the impact of alcohol on the progression and sequelae of SIV infection in rhesus monkeys as it relates to the primary infection itself and the development of secondary infections. It is our hypothesis that alcohol functions as a cofactor to accelerate the progression of SIV infection as well as to increase host susceptibility to opportunistic infections which, in turn, will further accelerate progression of SIV infection. This research tests this hypothesis by addressing 3 Specific Aims: 1) To determine the effect of alcohol consumption on primary infection with SIV, progression of SIV infection, and the subsequent development of opportunistic infections. 2) To examine in vivo the separate and combined effects of alcohol consumption and SIV infection on the innate immune system of the lung. 3) To determine the in vivo effect of alcohol consumption on indices of SIV disease progression in response to experimental intrapulmonary infection. Addressing these specific aims in the context of a well-defined and accepted nonhuman primate model of HIV infection will provide novel and important information on the effects of alcohol on altering host defenses to both primary infection with HIV and its progression.