ALCOHOL, SIV INFECTION AND HOST DEFENSE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心赠款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 背景：酗酒和HIV感染是常见的，并且经常在同一个体中共存。 该项目测试了酒精作为辅助因子加速SIV感染进展的假设，并增加宿主对机会性感染的易感性，这将进一步加速疾病进展。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，研究肺炎对SIV表达的影响，并研究酒精对SIV感染恒河猴抗逆转录病毒治疗的疗效和毒性的影响。 研究方法：24只恒河猴已通过手术植入胃导管，以在方案期间给予乙醇或蔗糖（对照受试者）。动物在开始酒精后3个月感染SIVmac 251，并在SIV接种后4个月感染肺炎链球菌。一些动物在SIV感染2个月时开始接受抗逆转录病毒药物。在选定的时间采集血样和支气管肺泡灌洗。 结果/讨论：酒精处理增加了血浆病毒设定点。对SIV特异性CD 4+和CD 8 + T细胞应答以及抗SIV抗体应答的分析未能显示SIV特异性免疫应答与病毒载量之间的关联。在肺部感染的反应中，在蔗糖和酒精处理的动物中，在BAL液中回收的SIV拷贝增加。与蔗糖动物相比，酒精动物的增加持续时间更长（14天vs 1天）。这些研究表明，酒精滥用可能会加速疾病进展，部分原因是抑制宿主对感染的防御，并延长对机会性感染的病毒产生的上调。已经开始研究酒精对粘膜宿主防御、疾病传播、肺宿主防御、造血和存在和不存在肌肉萎缩的肌肉萎缩的影响。

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.