Detection and cellular localization of enterovirus RNA sequences in spinal cord of patients with ALS
Detection and cellular localization of enterovirus RNA sequences in spinal cord of patients with ALS
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DOI：
10.1212/wnl.54.1.20
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发表时间：
2000-01-11
期刊：
影响因子：
9.9
通讯作者：
Lina, B
中科院分区：
文献类型：
--
作者：
Berger, MM;Kopp, N;Lina, B
目的：探讨肠道病毒（EV）持续感染与肌萎缩侧索硬化症（ALS）发病的关系。背景：虽然ALS是一种临床上定义明确的运动神经元疾病，但对散发病例的病因和发病机制知之甚少。在已经假设的不同原因中，关于持续性肠道病毒感染的可能作用的报告结果相互矛盾。研究方法：对17例确诊ALS患者和29例无运动神经元病史的对照组脊髓标本进行逆转录酶PCR（RT-PCR）和直接RT-原位PCR（RT-IS-PCR）。当获得时，随后对PCR产物进行测序。结果如下：使用直接RT-IS-PCR，在17例ALS患者中的15例（88.3%）中检测到EV核酸序列，而29例对照受试者中的1例（3.4%）。PCR产物位于脊髓前角的神经元细胞体中。17例ALS患者中有13例的RT-PCR产物与埃可病毒7型的同源性在94%~ 86%之间。结论：ALS患者脊髓灰质内神经元细胞体中肠道病毒（EV）核酸的检出率为88.3%，这强烈表明持续性EV RNA与ALS之间存在关联。需要进一步的工作来证实我们检测到的持续EV序列在某种程度上参与了ALS的发展。
Objective: To investigate the possible association of persistent enterovirus (EV) infection with the development of ALS. Background: Although ALS is a clinically well-defined motor neuron disease, little is known about the etiology and pathogenesis of the sporadic cases. Among the different causes that have been hypothesized, conflicting results have been reported about the possible role of persistent enteroviral infection. Methods: Reverse transcriptase-PCR (RT-PCR) and direct RT in situ PCR (RT-IS-PCR) were performed in formaldehyde-fixed spinal cord samples of 17 patients with confirmed ALS and 29 control subjects with no history of motor neuron disease. When obtained, PCR products were sequenced subsequently. Results: Using direct RT-IS-PCR, EV nucleic acid sequences were detected in 15 (88.3%) of 17 patients with ALS compared to 1 (3.4%) of 29 control subjects. PCR products were located in neuronal cell bodies of the anterior horns of the spinal cord. The RT-PCR products obtained in 13 of the 17 patients with ALS showed between 94% and 86% homology with echovirus 7 sequences. Conclusion: The 88.3% rate of detection of enterovirus (EV) nucleic acids in the neuronal cell bodies within the gray matter of the spinal cord of patients with ALS strongly suggests association between persistent EV RNA and ALS. Further work is required to confirm that the persisting EV sequences we detected are somehow involved in the develop ment of ALS.