ALCOHOL, SIV INFECTION AND HOST DEFENSE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 背景：酗酒和HIV感染是很常见的，而且经常在同一个人身上共存。该项目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，这将进一步加速疾病的进展。本研究的目的是通过检测SIV的宿主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感染猕猴抗逆转录病毒治疗的疗效和毒性的影响。方法：对24只恒河猴进行手术置入胃管，在实验期间给予乙醇或蔗糖(对照组)。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。一些动物在感染SIV的2个月时开始接受抗逆转录病毒药物治疗。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CD4和CD8 T细胞反应和抗SIV抗体反应的分析未能显示SIV特异性免疫反应与病毒载量之间的关联。作为对肺部感染的反应，蔗糖和酒精处理的动物在BAL液中恢复的SIV拷贝数都增加了。与蔗糖动物相比，酒精动物的增加持续时间更长(14天比1天)。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。已经开始研究酒精对粘膜宿主防御、疾病传播、肺宿主防御、造血和肌肉萎缩的影响，同时存在和不存在肌肉萎缩。

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.