ALCOHOL, SIV INFECTION AND HOST DEFENSE

酒精、SIV 感染和宿主防御

• 批准号: 8358027
• 负责人: STEVE NELSON
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358027
• 关键词: Alcohol abuse; Alcohols; Alveolar; Animals; Anti-Retroviral Agents; Antibody Formation; Blood specimen; CD8B1 gene; Catheters; Disease Progression; Ethanol; Funding; Grant; HIV Infections; Hematopoiesis; Host Defense; Immune response; Implant; Individual; Infection; Irrigation; Liquid substance; Lung; Macaca mulatta; Methods; Muscle; National Center for Research Resources; Opportunistic Infections; Pharmaceutical Preparations; Plasma; Pneumonia; Predisposition; Primates; Principal Investigator; Production; Protocols documentation; Research; Research Infrastructure; Resources; SIV; Source; Stomach; Streptococcus pneumoniae; Sucrose; T cell response; Testing; Time; Toxic effect; United States National Institutes of Health; Up-Regulation; Viral; Viral Load result; Virus; alcohol abuse therapy; alcohol effect; antiretroviral therapy; cofactor; cost; defense response; disease transmission; response; wasting

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. Background: Alcohol abuse and HIV infection are common and frequently coexist in the same individual. This project tests the hypothesis that alcohol functions as a cofactor to accelerate the progression of SIV infection, and to increase host susceptibility to opportunistic infections which will further accelerate disease progression. The purposes are to identify mechanisms by which alcohol impacts SIV disease progression by examining the host defense response to SIV, to study the effect of pneumonia on SIV expression, and to study the impact of alcohol on the efficacy and toxicity of antiretroviral therapy in SIV infected rhesus macaques. Methods: 24 rhesus macaques have had gastric catheters surgically implanted to administer either ethanol or sucrose (control subjects) for the duration of a protocol. Animals were infected with SIVmac251 3 months after starting alcohol and infected with Streptococcus pneumoniae 4 months after SIV inoculation. Some animals started to receive antiretroviral drugs at 2 months of SIV infection. Blood samples and bronchial alveolar lavage were obtained at selected times. Results/Discussion: Alcohol treatment increased plasmas viral set point. Analysis of SIV-specific CD4+ and CD8+ T cell response and anti-SIV antibody response failed to show an association between SIV-specific immune responses and viral load. In response to lung infection, SIV copies recovered in BAL fluid was increased in both sucrose and alcohol treated animals. The duration of the increase was greater in alcohol compared to sucrose animals (14 days vs 1 day). These studies indicate that alcohol abuse may accelerate disease progression, in part, by suppressing host defense against the infection and prolonging up regulation of virus production in response to an opportunistic infection. Studies have been initiated to examine the effect of alcohol on mucosal host defense, disease transmission, lung host defense, hematopoiesis, and muscle wasting in the presence and absence of muscle wasting.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 背景：酗酒和艾滋病毒感染很常见，并且经常在同一个人中共存。 该项目检验了酒精作为辅助因子加速SIV感染进展的假设，并增加了宿主对机会性感染的敏感性，这将进一步加速疾病的进展。目的是通过检查宿主对SIV的宿主防御反应，研究肺炎对SIV表达的影响，并研究酒精对SIV感染鼠尾草的抗逆转录病毒疗法对抗逆转录病毒疗法的疗效和毒性的影响。 方法：在协议期间，有24个恒河猕猴已通过手术植入胃导管来植入乙醇或蔗糖（对照组）。 SIV接种后4个月，入饮酒后3个月3个月感染了动物SIVMAC251，并感染了肺炎链球菌。一些动物在2个月的SIV感染时开始接受抗逆转录病毒药物。在选定时间获得血液样本和支气管肺泡灌洗。 结果/讨论：酒精治疗增加了血浆病毒设定点。 SIV特异性CD4+和CD8+ T细胞反应和抗SIV抗体反应的分析未显示SIV特异性免疫反应与病毒载量之间的关联。为了应对肺部感染，蔗糖和酒精治疗的动物在BAL液中回收的SIV副本均增加。与蔗糖动物相比，酒精的增加持续时间更大（14天比1天）。这些研究表明，酗酒可能部分通过抑制宿主防御感染并延长了对机会性感染的病毒产生的调节。已经开始研究，以检查酒精对粘膜宿主防御，疾病传播，肺部防御，造血和肌肉浪费的影响。