Detection of the human immunodeficiency virus regulatory protein tat in CNS tissues
Detection of the human immunodeficiency virus regulatory protein tat in CNS tissues
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DOI：
10.3109/13550280009013158
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发表时间：
2000-04-01
影响因子：
3.2
通讯作者：
Everall, I
中科院分区：
文献类型：
--
作者：
Hudson, L;Liu, JK;Everall, I
在神经病理学上，人类免疫缺陷病毒（HIV）与一系列炎性疾病、广泛的皮质神经元损失以及树突和突触损伤相关。虽然导致这些异常的机制尚不清楚，但神经毒性作用被认为部分是由于病毒产物，包括达特基因产物。我们以前已经表明，达特当呈现给神经元细胞外与神经元细胞膜相互作用，引起神经元兴奋和毒性的fmol量。为探讨达特在HIV脑炎（HIVE）中的作用，我们检测了9例HIVE患者和7例非HIVE患者的组织提取物中的tot mRNA和蛋白。尽管尸检时间长，降解显著，但在4/9例HIVE患者中检测到tot mRNA，但在7例无痴呆患者中未检测到tot mRNA。同样，5/9例HIVE患者也检测到env mRNA，而非HIVE患者则未检测到。然而，在有（5/9）或无（2/7）HIVE的两组患者中均检测到vif mRNA。使用来自同一组患者的脑蛋白提取物，我们不能用酶联免疫吸附测定（ELISA）检测达特（灵敏度为2ng达特/ml脑组织）。然而，达特可以通过化学方法和从患有脑炎的恒河猴脑中提取的蛋白质中检测到，这些脑炎是由于HIV和猿免疫缺陷病毒（SHIV）的嵌合株引起的。我们的观察支持达特在HIV和SHIV脑炎的神经发病机制中的作用。
Neuropathologically, human immunodeficiency virus (HIV) is associated with a range of inflammatory disorders, extensive cortical neuronal loss, and dendritic and synaptic damage. Although the mechanisms resulting in these abnormalities are still unclear, the neurotoxic effects are thought to be due in part to viral products including the tat gene product. We have previously shown that Tat when presented to neurons extracellularly interacts with neuronal cell membranes to cause neuronal excitation and toxicity in fmole amounts. To determine the role of Tat in mediating HIV encephalitis (HIVE), we detected tot mRNA and protein in tissue extracts of nine patients with HIVE and seven patients without HIVE. Despite long autopsy times and significant degradation, tot mRNA was detected in 4/9 patients with HIVE but not in any of the seven patients without dementia. Similarly, the env mRNA was also detected in 5/9 patients with HIVE but not in the patients without HIVE. However, vif mRNA was detected in both groups of patients with (5/9) or without (2/7) HIVE, Using protein extracts from the brains of the same groups of patients we were unable to detect Tat by enzyme linked immunosorbant assay (ELISA) (sensitivity of 2 ng Tat/ml of brain tissue). However, Tat could be detected immunohistochemically and in protein extracts from the brains of rhesus macaques with encephalitis due to a chimeric strain of HIV and simian immunodeficiency virus (SHIV). Our observations support the role of Tat in the neuropathogenesis of HIV and SHIV encephalitis.