先天性CMV感染致中枢神经系统畸形发育机制

胎儿中枢神经系统(central nervous system,CNS)是人类巨细胞病毒(human cytomegalovirus,HCMV)先天性感染的主要靶器官。胚胎期CMV感染常常导致严重CNS畸形的发生,其前提条件是CNS中的神经前体(干)细胞、神经元及神经胶质细胞对CMV普遍易感。发育期CNS感染CMV具有以下特点:⑴神经系统细胞对CMV的容纳性在CNS的不同发育阶段有所不同;⑵受累的细胞数随着发育的进展而增多;⑶CNS不同部位的细胞对CMV的敏感性存在明显的差异;⑷感染发生时细胞所处细胞周期的时相也与感染严重程度密切相关。CMV感染能诱导宿主细胞特异性的染色体折断,影响Homeobox基因(胚胎发育的主控基因)的表达,进而阻断细胞周期(G1期滞留)、诱导细胞凋亡,导致CNS细胞数量减少与迁徙异常,最终导致C N S发育畸形。

Fetal central nervous system anomalies induced by congenital cytomegalovirus infection

Fetal central nervous system(CNS) is the main target organ of congenital human cytomegalovirus(HCMV) infection.And this infection in embryo can lead to severe CNS anomalies.In the CNS,the permissive-ness of the neural stem cells,neurons and glial cells to CMV is the precondition determining the degree of the congenital CNS anomalies.We can summarize several characteristics of the infection: first,the permissiveness of the developing brain cells to CMV differes;second,the number of the infected cells increases obviously with the develepment of the brain;third,the susceptibility of the CNS to CMV is different in different parts of the CNS;and finally when infected,the phase in the cell cycle is also a vital factor affecting the severity of the infection.CMV infection can induce specific chromosome breakages,thereby affecting Homeobox genes ex-pression in host cell,causing cell cycle arrest,and leading to cell apoptosis.These changes would decrease the number of normal nerve cells and result in mis-migration of the cells and finally cause malformation of CNS.