Eash Sylvia, Tavares Rosemarie, Stopa Edward G, Robbins Scott H, Brossay Laurent, Atwood Walter J
Department of Molecular Microbiology and Immunology, and Graduate Program in Pathobiology, Rhode Island Hospital, Brown University, Providence, Rhode Island 02912, USA.
Am J Pathol. 2004 Feb;164(2):419-28. doi: 10.1016/S0002-9440(10)63132-X.
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 alpha 2,6-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 alpha 2-6-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.
JC病毒（JCV）是多瘤病毒家族的成员，可导致人类中枢神经系统（CNS）发生脱髓鞘疾病，即进行性多灶性白质脑病。尽管在进行性多灶性白质脑病患者中，神经胶质细胞是JCV生产性感染的主要靶细胞，但关于JCV的潜伏部位以及病毒传播至中枢神经系统导致疾病的机制，人们知之甚少。此前的研究表明，在外周血、扁桃体和脾脏的B淋巴细胞中存在复制的JCV DNA，并且有人推测淋巴细胞可能是JCV的潜伏部位之一。在肾小管中检测到病毒基因产物以及尿液中排出JC病毒粒子，提示JCV可潜伏于肾脏。也有人推测病毒通过呼吸道传播，这意味着肺是JCV持续感染的另一个可能部位。我们实验室早期的研究表明，末端α2,6连接的唾液酸是JCV受体的关键组成部分。在本报告中，我们检测了这种JCV受体型唾液酸在一组正常人体组织中的组织分布。我们的结果表明，在正常大脑中，JCV受体型唾液酸在少突胶质细胞和星形胶质细胞上表达，但在皮质神经元上不表达。在正常人体脾脏和扁桃体中，受体型唾液酸在B淋巴细胞上的表达也高于T淋巴细胞。此外，肾脏和肺均表达大量的α2-6连接唾液酸。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相关性。这些发现也支持了JCV潜伏于淋巴组织以及B细胞促进病毒向中枢神经系统传播的假说。
