Apoptosis induced by HIV-1 infection of the central nervous system.
Apoptosis induced by HIV-1 infection of the central nervous system.
复制标题
HIV-1感染中枢神经系统诱导细胞凋亡。
DOI：
10.1172/jci119002
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Gabuzda,D
中科院分区：
文献类型：
--
作者：
Shi,B;DeGirolami,U;He,J;Wang,S;Lorenzo,A;Busciglio,J;Gabuzda,D
细胞凋亡在免疫系统中的艾滋病发病机制中起作用，但其在HIV-1诱导的神经系统疾病中的作用尚不清楚。在这项研究中，我们研究细胞凋亡诱导的HIV-1感染的中枢神经系统（CNS）在体外模型和艾滋病患者的脑组织。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）和碘化丙啶染色以及电子显微镜测定，原代脑培养物的HIV-1感染在体外诱导神经元和星形胶质细胞凋亡。细胞凋亡没有显着诱导，直到1-2周后的时间病毒生产高峰，这表明诱导可溶性因子，而不是直接病毒感染。10/11例AIDS患者脑组织中也检测到神经元和星形胶质细胞凋亡，其中5/5例HIV-1痴呆患者和4/5例非痴呆患者。此外，在艾滋病患者的脑中经常检测到内皮细胞凋亡，并通过电子显微镜证实。大多数凋亡细胞不定位于HIV-1感染的细胞附近，这为可溶性因子的诱导提供了进一步的证据。在6名非艾滋病对照患者的正常大脑中，凋亡细胞不存在或仅限于罕见的星形胶质细胞。然而，TUNEL阳性神经元和星形胶质细胞频繁检测到7例阿尔茨海默病或丰富的老年斑。这些研究表明，细胞凋亡是艾滋病中枢神经系统损伤的一种机制，可能是由可溶性因子诱导的。CNS中内皮细胞的凋亡提高了这些因子中的一些可能是血液来源的可能性。
Apoptosis plays a role in AIDS pathogenesis in the immune system, but its role in HIV-1-induced neurological disease is unknown. In this study, we examine apoptosis induced by HIV-1 infection of the central nervous system (CNS) in an in vitro model and in brain tissue from AIDS patients. HIV-1 infection of primary brain cultures induced apoptosis in neurons and astrocytes in vitro as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and propidium iodide staining and by electron microscopy. Apoptosis was not significantly induced until 1-2 wk after the time of peak virus production, suggesting induction by soluble factors rather than by direct viral infection. Apoptosis of neurons and astrocytes was also detected in brain tissue from 10/11 AIDS patients, including 5/5 patients with HIV-1 dementia and 4/5 nondemented patients. In addition, endothelial cell apoptosis was frequently detected in the brain of AIDS patients and was confirmed by electron microscopy. Most of the apoptotic cells were not localized adjacent to HIV-1-infected cells, providing further evidence for induction by soluble factors. In six non-AIDS control patients with normal brain, apoptotic cells were absent or limited to rare astrocytes. However, TUNEL-positive neurons and astrocytes were frequently detected in seven patients with Alzheimer's disease or abundant senile plaques. These studies suggest that apoptosis is a mechanism of CNS injury in AIDS which is likely to be induced by soluble factors. The apoptosis of endothelial cells in the CNS raises the possibility that some of these factors may be blood-derived.