Differential distribution of the JC virus receptor-type sialic acid in normal human tissues
Differential distribution of the JC virus receptor-type sialic acid in normal human tissues
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DOI：
10.1016/s0002-9440(10)63132-x
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发表时间：
2004-02-01
影响因子：
6
通讯作者：
Atwood, WJ
中科院分区：
文献类型：
--
作者：
Eash, S;Tavares, R;Atwood, WJ
JC病毒（JCV）是多瘤病毒家族的一员，可引起人类中枢神经系统（CNS）的脱髓鞘疾病，称为进行性多灶性白质脑病。尽管胶质细胞是进行性多灶性白质脑病患者中JCV生产性感染的主要目标，但关于JCV持续存在的部位以及病毒传播到中枢神经系统引起疾病的机制知之甚少。先前的工作已经证明了外周血、扁桃体和脾脏的B淋巴细胞中存在复制的JCV DNA，并且已经假设淋巴细胞可能是JCV持续存在的一个位点。肾小管中病毒基因产物的检测和尿液中JC病毒体的排泄表明JCV在肾脏中的持续存在。还假设病毒传播的呼吸道途径涉及肺作为持续性JCV感染的另一个可能部位。我们实验室的早期研究表明，末端α 2，6-连接的唾液酸是JCV受体的关键组分。在这份报告中，我们研究了这种JCV受体型唾液酸在一组正常人体组织中的组织分布。我们的研究结果表明，在正常的大脑中，JCV受体型唾液酸的表达少突胶质细胞和星形胶质细胞，但不对皮质神经元。受体型唾液酸在正常人脾脏和扁桃体中的B淋巴细胞上的表达也比T淋巴细胞高。此外，肾和肺都表达大量的α 2 -6-连接的唾液酸。我们的数据显示，细胞上JCV受体型唾液酸的表达与其对病毒感染的易感性之间存在显著的相关性。这些发现也支持JCV在淋巴组织中持续存在和B细胞促进病毒传播至CNS的假设。
JC virus (JCV), a member of the polyomavirus family, causes a demyelinating disease of the central nervous system (CNS) in humans known as progressive multifocal leukoencephalopathy. Although glial cells are the principal target of JCV productive infection in progressive multifocal leukoencephalopathy patients, little is known regarding the site of JCV persistence and the mechanisms by which the virus spreads to the CNS to cause disease. Previous work has demonstrated the presence of replicating JCV DNA in B lymphocytes from peripheral blood, tonsil, and spleen and it has been hypothesized that lymphocytes may be one site of JCV persistence. Detection of viral gene products in renal tubules and excretion of JC virions in the urine suggests JCV persistence in the kidney. A respiratory route of viral transmission has also been hypothesized implicating the lung as another possible site of persistent JCV infection. Earlier studies from our laboratory have shown that terminal alpha2,6-linked sialic acid is a critical component of the JCV receptor. In this report we examined the tissue distribution of this JCV receptor-type sialic acid in a panel of normal human tissues. Our results demonstrate that in normal brain JCV receptor-type sialic acids are expressed on oligodendrocytes and astrocytes, but not on cortical neurons. The receptor-type sialic acid is also more highly expressed on B lymphocytes than on T lymphocytes in normal human spleen and tonsil. in addition, both the kidney and lung express abundant levels of alpha2-6-linked sialic acids. Our data show a striking correlation between the expression of the JCV receptor-type sialic acid on cells and their susceptibility to infection by the virus. These findings also support the hypothesis of JCV persistence in lymphoid tissue and B-cell-facilitated viral dissemination to the CNS.