Tsutsui Yoshihiro, Kosugi Isao, Kawasaki Hideya
Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Rev Med Virol. 2005 Sep-Oct;15(5):327-45. doi: 10.1002/rmv.475.
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.
巨细胞病毒（CMV）是发育性脑疾病最常见的感染病因，也会导致免疫功能低下个体的脑损伤。尽管大脑是CMV感染的主要靶器官之一，但由于研究人类受试者存在局限性，人们对CMV在人类中引起的脑疾病的神经发病机制知之甚少。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方面与人类巨细胞病毒（HCMV）相似。在小鼠模型中，已表明神经干/祖细胞在发育中的大脑中对CMV感染最为敏感。在大脑发育过程中，裂解感染倾向于发生在未成熟的神经胶质细胞中，可能导致大脑结构紊乱。在感染的延长阶段，CMV优先感染神经元细胞。神经元感染可能通过逃避免疫反应、抗凋亡作用和e1启动子的神经元特异性激活而趋于持续，可能导致神经元功能紊乱。还表明，发育中大脑的CMV感染可能在神经未成熟细胞中潜伏。潜伏感染的重新激活可能在感染后很长时间发生脑疾病。
