Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain
Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain
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进行性多灶性白质脑病（JC 病毒引起的人脑脱髓鞘疾病）的发病机制和分子生物学
DOI：
10.1128/cmr.5.1.49
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发表时间：
1992
影响因子：
36.8
通讯作者：
J. Berger
中科院分区：
文献类型：
--
作者：
E. Major;K. Amemiya;C. Tornatore;S. Houff;J. Berger
JC病毒感染的发病机制和分子生物学的研究在过去的二十年中，显着改变了我们的理解进行性多灶性白质脑病，它可以被描述为一种亚急性病毒感染的神经胶质细胞，可能以下重新激活的潜伏感染，而不是延长JC病毒在大脑中复制的结果。现在有足够的证据表明，JC病毒潜伏期发生在肾脏和B细胞。然而，从脑或肾分离的JC病毒在其病毒基因组的调节区不同，其受宿主细胞因子控制以进行病毒基因表达和复制。病毒基因组非编码区的DNA序列在脑和肾分离株中显示出一定的异质性。这些数据表明，JC病毒存在一个原型株，其序列在不同细胞类型的复制过程中发生改变。JC病毒调节区可能在建立病毒潜伏期中起重要作用，并且必须对病毒的再活化起作用。一个发展中的假说是，再活化发生于潜伏感染的B淋巴细胞，这些淋巴细胞由于免疫抑制而被活化。JC病毒通过激活的B细胞进入大脑。这一机制的证据是在进行性多灶性白质脑病患者的外周血淋巴细胞和脑内受感染的B细胞中检测到JC病毒DNA。一旦病毒进入大脑，星形胶质细胞以及少突胶质细胞支持JC病毒增殖。因此，JC病毒感染的神经胶质细胞可能会损害其他神经胶质细胞的功能，除了髓鞘的生产和维护。因此，我们对进行性多灶性白质脑病发病机制的了解增加，提示了免疫调节治疗干预JC病毒感染的新方法。也许沿着核苷类似物或干扰素给药的试验，这种致命的疾病，对于抗病毒治疗还没有共识，可能会产生创新的治疗方案。
Studies of the pathogenesis and molecular biology of JC virus infection over the last two decades have significantly changed our understanding of progressive multifocal leukoencephalopathy, which can be described as a subacute viral infection of neuroglial cells that probably follows reactivation of latent infection rather than being the consequence of prolonged JC virus replication in the brain. There is now sufficient evidence to suggest that JC virus latency occurs in kidney and B cells. However, JC virus isolates from brain or kidney differ in the regulatory regions of their viral genomes which are controlled by host cell factors for viral gene expression and replication. DNA sequences of noncoding regions of the viral genome display a certain heterogeneity among isolates from brain and kidney. These data suggest that an archetypal strain of JC virus exists whose sequence is altered during replication in different cell types. The JC virus regulatory region likely plays a significant role in establishing viral latency and must be acted upon for reactivation of the virus. A developing hypothesis is that reactivation takes place from latently infected B lymphocytes that are activated as a result of immune suppression. JC virus enters the brain in the activated B cell. Evidence for this mechanism is the detection of JC virus DNA in peripheral blood lymphocytes and infected B cells in the brains of patients with progressive multifocal leukoencephalopathy. Once virus enters the brain, astrocytes as well as oligodendrocytes support JC virus multiplication. Therefore, JC virus infection of neuroglial cells may impair other neuroglial functions besides the production and maintenance of myelin. Consequently our increased understanding of the pathogenesis of progressive multifocal leukoencephalopathy suggests new ways to intervene in JC virus infection with immunomodulation therapies. Perhaps along with trials of nucleoside analogs or interferon administration, this fatal disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols.
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DOI：
10.1093/infdis/147.4.669
发表时间：
1983
期刊：
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影响因子：
--
作者：
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DOI：
10.1099/0022-1317-64-10-2271
发表时间：
1983
期刊：
The Journal of general virology
影响因子：
--
作者：
Martin,JD;Padgett,BL;Walker,DL
通讯作者：
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DOI：
10.1073/pnas.83.7.2271
发表时间：
1986
影响因子：
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作者：
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Webster,HD
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DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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通讯作者：
Khalili,K
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DOI：
--
发表时间：
1983
期刊：
Progress in clinical and biological research
影响因子：
--
作者：
Andrews,CA;Daniel,RW;Shah,KV
通讯作者：
Shah,KV