ALCOHOL, SIV INFECTION AND HOST DEFENSE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景：酒精滥用和人类免疫缺陷病毒（HIV）感染是常见的，往往同时存在于同一个人。 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，而HIV主要通过感染和消耗CD 4 T淋巴细胞来发挥其致病作用。 然而，酒精如何影响艾滋病毒疾病的传播，发病机制，进展和治疗知之甚少。本项目通过以下具体目的检验酒精作为辅助因子加速SIV感染进展以及增加宿主对机会性感染的易感性的假设：1）检验酒精通过损害病毒特异性T淋巴细胞应答而增加SIV感染猕猴中血浆病毒设定点的假设; 2）检验在肺炎球菌性肺炎期间SIV复制的上调通过饮酒而增强的假设; 3）检验肺中SIV复制的这种增加通过肺泡巨噬细胞中NF-κ B的活化而诱导的假设;和4）的方法为了检验这一假设，即SIV在肺中增殖的增加导致新的SIV基因型的产生，所述新的SIV基因型与SIV在肺中增殖的增加相关。疾病进展。研究方法：目前，有25只恒河猴手术植入导管，用于在感染SIV后给予乙醇或蔗糖（对照受试者）溶液。 每周一次在麻醉下检查所有动物，并在那时收集样品。 结果：初步数据显示，酒精不会改变对SIV感染的CD 8+特异性反应。然而，正在进行的研究表明，酒精可能会增加SIV存在于支气管肺泡灌洗液（BALF）4个月PI，并增加SIV的生产与肺炎球菌的肺挑战，部分增加核NF-κ B。结论：在一个明确定义和公认的非人灵长类HIV感染模型的背景下完成这些特定目标，将为酒精改变宿主对HIV原发感染及其进展的防御能力提供新的重要信息。

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. Background: 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, and HIV primarily exerts its pathogenic effects by infecting and depleting CD4 T lymphocytes. However, how alcohol impacts HIV disease transmission, pathogenesis, progression and treatment are poorly understood. This projects tests the 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 by addressing the following Specific Aims: 1) to test the hypothesis that alcohol increases the plasma viral set point in SIV infected macaques by compromising viral specific T lymphocyte responses; 2) to test the hypothesis that upregulation of SIV replication during pneumococcal pneumonia is enhanced by alcohol consumption; 3) to test the hypothesis that this increase in SIV replication in the lung is induced by activation of NF-kB in alveolar macrophages; and 4) to test the hypothesis that this increased of SIV proliferation in the lung results in the generation of new SIV genotypes that are associated with increased disease progression. Methods: Currently, 25 rhesus macaques have surgically implanted catheters used to administer either ethanol or sucrose (control subjects) solution after infection with SIV. All animals are examined under anesthesia once weekly and samples are collected at that time. Results: Preliminary data reveals that alcohol does not alter the CD8+ specific in response to SIV infection. However, ongoing studies show that alcohol may increase SIV presence in bronchoalveolar lavage fluid (BALF) 4 months PI, and increases SIV production in lungs challenge with pneumococcus by in part increasing nuclear NF-kB. Conclusion: Completing 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.