ALCOHOL, SIV INFECTION AND HOST DEFENSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：酒精滥用和人类免疫缺陷病毒(HIV)感染是常见的，并且经常在同一个体中共存。这项计划测试了酒精作为辅助因素加速SIV感染进展的假设，并增加了宿主对机会性感染的易感性，这反过来将进一步加速疾病的进展。目前的研究目的是通过检测宿主对SIV的防御反应来确定酒精影响SIV疾病进展的机制，并研究肺炎对SIV表达的影响。方法：为此，24只恒河猴接受了外科手术置入胃管的实验，以在实验期间给予乙醇或蔗糖(对照对象)。动物在开始饮酒3个月后感染SIVmac251，在接种SIV后4个月感染肺炎链球菌。在选定的时间段采集血样和进行支气管肺泡灌洗。结果/讨论：酒精治疗提高了血浆病毒的起始点。对SIV特异性的CD4+和CD8+T细胞反应和抗SIV抗体反应的分析正在进行中。在对肺部感染的反应中，蔗糖和酒精处理的动物在BAL液中恢复的SIV拷贝数增加，并伴随着核内核因子-kB的增加。与蔗糖动物相比，酒精增加的持续时间更长(14天比1天)。此外，还对留有较长胃管的动物进行了仔细的分析，这使我们能够改进导尿管的护理。这些研究表明，酗酒可能会加速疾病的进展，部分原因是抑制了宿主对感染的防御，并延长了对机会性感染的病毒产生的调节。对明确定义和被接受的非人类灵长类艾滋病毒感染模型的继续研究将为酒精对艾滋病毒疾病传播、发病机制、进展和治疗的影响提供新的和重要的信息。

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. 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.