Neuropathogenesis in cytomegalovirus infection: indication of the mechanisms using mouse models
Neuropathogenesis in cytomegalovirus infection: indication of the mechanisms using mouse models
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DOI：
10.1002/rmv.475
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发表时间：
2005-09
影响因子：
11.1
通讯作者：
Y. Tsutsui;I. Kosugi;H. Kawasaki
中科院分区：
文献类型：
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作者：
Y. Tsutsui;I. Kosugi;H. Kawasaki
巨细胞病毒(CMV)是最常见的发育性脑疾病的感染性原因，也会导致免疫受损的人的脑损伤。虽然大脑是CMV感染的主要靶点之一，但由于人类研究对象的局限性，对CMV引起的人类脑部疾病的神经发病机制知之甚少。小鼠巨细胞病毒(MCMV)在基因组结构、基因表达模式、细胞嗜性和感染动态等方面与人巨细胞病毒(HCMV)相似。在小鼠模型中，研究表明，在发育中的大脑中，神经干细胞/祖细胞最容易受到CMV感染。在大脑发育过程中，溶血性感染往往发生在未成熟的神经胶质细胞中，可能会导致大脑结构紊乱。在感染的延长阶段，CMV优先感染神经细胞。神经元的感染可能通过逃避免疫反应、抗凋亡效应和神经元特异性的E1启动子的激活而变得持久，可能导致神经元功能障碍。研究还表明，在发育中的大脑中，CMV感染可能会潜伏在神经未成熟细胞中。脑部疾病可能在感染后很长一段时间内通过潜伏感染的重新激活而发生。版权所有©2005 John Wiley&Sons，Ltd.
Cytomegalovirus (CMV) is the most frequent infectious cause of developmental brain disorders and also causes brain damage in immunocompromised individuals. Although the brain is one of the main targets of CMV infection, little is known about the neuropathogenesis of the brain disorders caused by CMV in humans because of the limitations in studying human subjects. Murine CMV (MCMV) is similar to human CMV (HCMV) in terms of genome structure, pattern of gene expressions, cell tropism and infectious dynamics. In mouse models, it has been shown that neural stem/progenitor cells are the most susceptible to CMV infection in developing brains. During brain development, lytic infection tends to occur in immature glial cells, presumably causing structural disorders of the brain. In the prolonged phase of infection, CMV preferentially infects neuronal cells. Infection of neurons may tend to become persistent by evasion of immune reactions, anti‐apoptotic effects and neuron‐specific activation of the e1‐promoter, presumably causing functional neuronal disorders. It has also been shown that CMV infection in developing brains may become latent in neural immature cells. Brain disorders may occur long after infection by reactivation of the latent infection. Copyright © 2005 John Wiley & Sons, Ltd.