MODULATION OF SIMIAN AIDS BY OPIOIDS

阿片类药物对猿猴艾滋病的调节

• 批准号: 6116667
• 负责人: RONALD Y CHUANG
• 金额: $ 7.98万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116667
• 关键词: AIDS; Mammalia; animal tissue; communicable diseases; immunology; inflammation; lymphatic system; substance abuse related disorder; virus

Significance Characterized by a growing number of opportunities infections and diseases, AIDS develops as a result of viral-induced immunosuppression in a host infected with the Human Immunodeficiency Virus (HIV). Cells infected by HIV consist of mainly T lymphocytes and macrophages, which are largely responsible for maintaining cell-mediated immunity. Little has been done, however, to investigate the extent of infection in other types of immune cells, such as polymorphonuclear neutrophils (PMN). Objectives Rhesus monkeys infected with simian immunodeficiency virus (SIV) have been an excellent animal model for the study of HIV infection and human AIDS. The present study was undertaken to determine whether SIV can infect monkey-derived PMN. PMN pathogenesis was studied through an in vitro infection of healthy rhesus macaque PMN with the molecular clone SIVmac239. The intracellular alterations after the infection and the PMN cell viability associated with the programmed cell death (apoptosis) were also studied. Results Using the polymerase chain reaction (PCR) technique, we detected the presence of SIVmac239 DNA in rhesus macaque-derived PMN after 24 hrs of in vitro incubation of the cells with SIVmac239. Infection by SIVmac239 also down-regulates the expression of the bcl-2 apoptosis-blocking gene in the infected PMN. These SIVmac239 induced PMN intracellular alterations were correlated with an accelerated decrease in PMN viability over a period of 120 hrs compared to non-infected PMN. Evidence of chromatin condensation characteristic of programmed cell death (apoptosis) was also observed in SIVmac239-infected PMN. The results of this study provide a mechanism for the reduced chemotaxis/phagocytosis activities of PMN of SIVmac239-infected macaques and suggest that PMN is one of the target cells for SIVmac239 infection. Future Directions Additional studies examining other PMN cell parameters in the presence of SIVmac239 infections are currently under investigation. KEY WORDS rhesus monkeys, SIVmac239, PMN, apoptosis, AIDS FUNDING NIH Grant DA05901

以越来越多的机会为特点 感染和疾病，艾滋病的发展是由于病毒引起的 感染人类免疫缺陷病的宿主的免疫抑制 病毒（HIV）。 被HIV感染的细胞主要由T淋巴细胞组成 和巨噬细胞，它们主要负责维持 细胞免疫 然而，几乎没有进行调查， 其他类型免疫细胞的感染程度，例如 多形核中性粒细胞（PMN）。 目的恒河猴 感染猴免疫缺陷病毒（SIV）已经成为一种 是研究HIV感染和人类艾滋病的极好动物模型。 本研究旨在确定SIV是否能感染 猴源性PMN。 通过体外培养的方法研究了PMN的发病机制。 用分子克隆感染健康恒河猴中性粒细胞 SIVmac239. 感染后细胞内的变化和 PMN细胞活性与程序性细胞死亡相关 （凋亡）也进行了研究。 结果使用聚合酶链 利用PCR技术，我们检测了SIVmac 239 DNA的存在， 恒河猴来源的PMN在体外孵育24小时后， SIVmac 239细胞 SIVmac 239的感染也下调了 bcl-2凋亡阻断基因在感染的PMN中的表达。 这些SIVmac 239诱导的PMN细胞内改变与 在120小时内PMN活力加速下降 与未感染的PMN相比。 染色质凝聚的证据 还观察到程序性细胞死亡（凋亡）的特征 在SIVmac 239感染的PMN中。 这项研究的结果提供了一个 中性粒细胞趋化/吞噬活性降低的机制 SIVmac 239感染猕猴，提示PMN是靶点之一 SIVmac 239感染。 其他研究 在SIVmac 239存在下检查其他PMN细胞参数 目前正在调查感染情况。 关键词恒河猴 猴，SIVmac 239，中性粒细胞，凋亡，艾滋病基金NIH Grant DA 05901