ALCOHOL, SIV INFECTION AND HOST DEFENSE

酒精、SIV 感染和宿主防御

• 批准号: 7562250
• 负责人: STEVE NELSON
• 金额: $ 7.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562250
• 关键词: Address; Alcohol abuse; Alcohol consumption; Alcohols; Alveolar Macrophages; CD4 Positive T Lymphocytes; Cells; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Development; Evolution; Funding; Genotype; Grant; HIV; Host Defense; Host Defense Mechanism; Immune; Immunity; Immunologic Monitoring; Immunosuppressive Agents; Individual; Infection; Institution; Lung; Macaca; Macaca mulatta; Membrane; Modeling; NF-kappa B; Opportunistic Infections; Plasma; Pneumococcal Pneumonia; Predisposition; Research; Research Personnel; Resources; SIV; Source; T-Lymphocyte; Testing; United States National Institutes of Health; Up-Regulation; Variant; Viral; Virus Diseases; alcohol effect; cofactor; macrophage; nonhuman primate; novel; receptor; response; secondary infection

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 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 SIV replication is upregulated in alveolar macrophages (AM) during experimental pneumococcal pneumonia and this upregulation is enhanced by alcohol consumption; 3) to test the hypothesis that the increase in SIV replication induced by an opportunistic pulmonary infection and enhanced by alcohol is mechanistically associated with activation of NF-kB in AM; and 4) to test the hypothesis that the proliferation of SIV induced by an opportunistic infection and enhanced by alcohol results in the selective replication of macrophage-tropic SIV genotypes and contributes to the evolution of novel phenotypic and antigenic variants. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 酒精滥用和人类免疫缺陷病毒（HIV）感染很常见，并且经常在同一人群中共存。 长期以来，众所周知，饮酒会抑制先天和特定免疫的关键方面，从而增加宿主对感染的敏感性。 HIV感染主要对表达CD4膜受体的免疫细胞发挥致病作用，从而导致CD4+细胞的逐渐消耗，免疫监视，机会性感染和死亡损害。 当前，几乎没有关于这两个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/或继发机会感染的宿主防御机制的信息。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，因为它与原发性感染本身有关和继发感染的发展。 我们的假设是，酒精是加速SIV感染进展的辅助因子，并增加了宿主对机会性感染的敏感性，进而将进一步加速SIV感染的进展。这项研究通过解决以下特定目的来检验该假设：1）检验以下假设：酒精通过损害病毒特异性T淋巴细胞反应来增加SIV感染猕猴的血浆病毒设定点； 2）测试假说，即在实验性肺炎球菌肺炎期间肺泡巨噬细胞（AM）中SIV复制的上调，并且通过酒精消耗增强了这种上调； 3）检验以下假设：机会性肺部感染引起的SIV复制增加并通过酒精增强与AM中NF-KB的激活相关； 4）为了检验以下假设：SIV诱导的机会性感染并通过酒精增强的假设会导致巨噬细胞 - 热带SIV基因型的选择性复制，并有助于新型表型和抗原变异的进化。在定义明确和公认的非人类灵长类动物模型的艾滋病毒感染模型的背景下解决这些特定目标将提供有关酒精对hiv及其艾滋病毒原发性感染及其进展的宿主防御措施影响的新颖和重要信息。