ALCOHOL, SIV INFECTION AND HOST DEFENSE

酒精、SIV 感染和宿主防御

• 批准号: 7958572
• 负责人: STEVE NELSON
• 金额: $ 5.81万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958572
• 关键词: Alcohol abuse; Alcohols; Alveolar; Animals; Antibody Formation; Blood specimen; CD8B1 gene; Caring; Catheters; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Ethanol; Funding; Grant; HIV; Host Defense; Implant; Individual; Infection; Institution; Irrigation; Liquid substance; Lung; Macaca mulatta; Methods; Modeling; NF-kappa B; Nuclear; Opportunistic Infections; Pathogenesis; Plasma; Pneumonia; Predisposition; Primates; Production; Protocols documentation; Research; Research Personnel; Resources; SIV; Source; Stomach; Streptococcus pneumoniae; Sucrose; T-Lymphocyte; Testing; Time; United States National Institutes of Health; Up-Regulation; Viral; Virus; Virus Diseases; alcohol abuse therapy; alcohol effect; cofactor; defense response; disease transmission; improved; nonhuman primate; novel; response

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. This projects 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, in turn, will further accelerate disease progression. The purposes of current studies are to identify mechanisms by which alcohol impacts SIV disease progression by examining the host defense response to SIV, and to study the effect of pneumonia on SIV expression. Methods: For this, 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. 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 is ongoing. In response to lung infection, SIV copies recovered in BAL fluid was increased in both sucrose and alcohol treated animals in association with an increase in nuclear NF-kB. The duration of the increase was greater in alcohol compared sucrose animals (14 days vs 1 day). In addition, a careful analysis of animals with prolonged gastric catheters was carried out which allowed us to improve catheter care. 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. Continued studies with a well-defined and accepted nonhuman primate model of HIV infection will provide novel and important information on the effects of alcohol on HIV disease transmission, pathogenesis, progression and treatment.

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。 背景：酗酒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。 该项目检验了以下假设：酒精是加速SIV感染进展的辅助因子，并增加宿主对机会性感染的敏感性，而机会性感染又将进一步加速疾病的进展。当前研究的目的是确定酒精通过检查宿主防御对SIV的反应并研究肺炎对SIV表达的影响，从而确定酒精会影响SIV疾病进展的机制。 方法：为此，在协议期间，有24个恒河猕猴已通过手术植入胃导管，以植入乙醇或蔗糖（对照对象）。 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。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细胞反应以及抗SIV抗体反应的分析正在进行中。为了应对肺部感染，在蔗糖和酒精治疗的动物中均增加了在BAL液中回收的SIV副本，并增加了核NF-KB的增加。与蔗糖动物相比，酒精的增加持续时间更大（14天比1天）。此外，对具有长时间胃导管的动物进行了仔细的分析，从而使我们能够改善导管护理。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。继续研究艾滋病毒感染的明确和接受的非人类灵长类动物模型将提供有关酒精对HIV疾病传播，发病机理，进展和治疗的影响的新颖和重要信息。