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An teratological experimental study of brain abnormalities induced by intrauterine infection with cytomegalovirus

巨细胞病毒宫内感染致脑畸形的畸形学实验研究

基本信息

批准号：
06671173
负责人：
TSUTSUI Yoshihito
金额：
$ 1.09万
依托单位：
Hamamatsu University School of medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The susceptibility of mice at different developmental stages to a relatively low titer of cell culuture-passeged murine cytomegalovirus (MCMV) infection was compared in terms of the urinary excretion of MCMV examined by plaque assay and in terms of the distribution of viral infection, determned by immunohistochemistry, using antibodies specific to the early nuclear antigenof MCMV.Viral infection on day 8.5 of getation (E8.5) into the conceptus and intraperitoneal infection on day 15.5 of gestation (E15.5), postnatal day 2 (P2), postnatal day 11 (P11), and 30 days after birth (P30), respectively, were performed. Embryonal and perinatal mice were more susceptible to MCMV in terms of urinary excretion of the virus and the presence of viral antigen-positive cells in the brain, lungs, and kidneys. In the embryonal and perinatal infection, the viral antigen-positive cells in the neurons of the cerebral cortex and hippocampus were retained late after birth, even though the positive cells in the lungs and kidneys had disappeared. In the mice infected on E8.5, small clusters of viral antigen-positive cells were detected only in the cortex and hippo-campus late after birth, without the urinary excretion of virus. These results suggest that when mice are infected with MCMV at the embryonal and perinatal stages, elimination of the infected neurons is delayd compared with that of the other cells in the lungs and kidneys. These findings provide a model for the anyalysis of pathogenesis of the subclinical congenital CMV infection that manifested clinically late after birth in humans as brain disorders.

本文比较了不同发育阶段小鼠对低滴度细胞培养传代的鼠巨细胞病毒（MCMV）感染的敏感性。用MCMV早期核抗原特异性抗体，于妊娠第8.5天进行病毒感染分别于妊娠15.5天（E15.5）、生后2天（P2）、生后11天（P11）和生后30天（P30）进行腹腔感染。胚胎和围产期小鼠更容易受到MCMV的尿排泄的病毒和病毒抗原阳性细胞在大脑中的存在，肺，和肾脏。在胚胎和围产期感染中，大脑皮层和海马神经元中的病毒抗原阳性细胞在出生后很晚才保留下来，尽管肺和肾中的阳性细胞已经消失。在E8.5感染的小鼠中，仅在出生后晚期的皮质和腹-腹中检测到小簇的病毒抗原阳性细胞，而没有病毒的尿排泄。这些结果表明，当小鼠在胚胎期和围产期感染MCMV时，与肺和肾中的其他细胞相比，受感染的神经元的消除被延迟。这些发现为分析亚临床先天性CMV感染的发病机制提供了一个模型，该感染在人类出生后晚期临床表现为脑部疾病。