Tsutsui Y
Second Department of Pathology, Hamamatsu University School of Medicine.
Nihon Rinsho. 1998 Jan;56(1):90-6.
Cytomegalovirus(CMV) is the most common infectious cause of congenital anomalies of the central nervous system(CNS) caused by intrauterine infection in humans. Since studies of human subjects have obvious limitation and CMV have strict species specificity, we have developed model systems for brain abnormalities induced by infection of mouse embryos with murine CMV (MCMV) which has similarities in structure and biology to human CMV (HCMV). We have previously reported that brain abnormalities, such as microphthalmia and brain atrophy, can be induced in mouse embryo by injection MCMV in to the conceptus at mid gestation. We have also showed that neurotropic feature of MCMV are prominent and that viral antigens in neuronal cells are also observed for a prolonged time following infection. We showed the evidences which suggest that MCMV may persistently infect in neuronal cells, whereas lytic infection may preferentially occur in glial cell in the developing brain. Disturbance of the neuronal migration and loss of neurons were reported to occur postnatally in the brains of MCMV-infected mice. Furthermore, MCMV infection induces apoptosis in uninfected neurons, and blocks and induction of apoptosis of primary neuronal cultures. These viral effect on the induction and blocking neuronal apoptosis, resulting in persistent infection, may be important for pathogenesis of morphological and functional brain disorders caused by congenital CMV infection in humans.
巨细胞病毒（CMV）是人类宫内感染导致中枢神经系统（CNS）先天性异常最常见的感染原因。由于对人类受试者的研究存在明显局限性，且CMV具有严格的种属特异性，我们开发了小鼠胚胎感染鼠巨细胞病毒（MCMV）诱导脑异常的模型系统，MCMV在结构和生物学特性上与人类巨细胞病毒（HCMV）相似。我们之前报道过，在妊娠中期将MCMV注射到孕体中可在小鼠胚胎中诱导脑异常，如小眼症和脑萎缩。我们还表明，MCMV的嗜神经性特征显著，且感染后很长一段时间内也能在神经元细胞中观察到病毒抗原。我们展示的证据表明，MCMV可能持续感染神经元细胞，而在发育中的大脑中，溶细胞性感染可能优先发生在神经胶质细胞中。据报道，MCMV感染的小鼠出生后大脑中会出现神经元迁移紊乱和神经元丢失现象。此外，MCMV感染可诱导未感染神经元发生凋亡，并阻断原代神经元培养物的凋亡诱导。这些病毒对神经元凋亡的诱导和阻断作用导致持续感染，这可能对人类先天性CMV感染所致脑形态和功能障碍的发病机制具有重要意义。
