Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus
Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus
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DOI：
10.1016/s0042-6822(03)00110-7
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发表时间：
2003-06-20
期刊：
影响因子：
3.7
通讯作者：
Griffin, DE
中科院分区：
文献类型：
--
作者：
Kimura, T;Griffin, DE
中枢神经系统的病毒感染和对这些感染的免疫反应引起多种神经系统疾病。辛德毕斯病毒感染断乳小鼠可引起急性非致死性脑脊髓炎，随后感染性病毒被清除，但病毒RNA持续存在。辛德毕斯病毒（NSV）的神经适应株的感染导致致命的脑脊髓炎，但感染后免疫血清的被动转移保护免受致命疾病和感染性病毒被清除。为了确定持续的NSV RNA是否与神经损伤相关，我们检查了恢复小鼠的大脑，发现海马回、邻近的白色物质和与单核细胞浸润相关的深层大脑皮质的进行性丧失。缺乏CD 4（+）T细胞的小鼠表现出较少的组织损失，而缺乏CD 8（+）T细胞的小鼠表现出与免疫活性小鼠相当的病变。缺乏CD 4（+）和CD 8（+）T细胞的小鼠出现了与免疫活性小鼠相似的严重组织损失，这与巨噬细胞的广泛浸润有关。海马回浸润的CD 4（+）细胞和巨噬细胞/小胶质细胞（而非CD 8（+）细胞）数量与末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性锥体神经元数量相关。这些结果表明，CD 4（+）T细胞可以促进进行性神经元死亡和组织损伤，尽管感染性病毒的清除。(C)2003 Elsevier Science（美国）。All rights reserved.
Viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. Infection of weanling mice with Sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral RNA. Infection with a neuroadapted strain of Sindbis virus (NSV) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. To determine whether persistent NSV RNA is associated with neurological damage, we examined the brains of recovered mice and found progressive loss of the hippocampal gyrus, adjacent white matter, and deep cerebral cortex associated with mononuclear cell infiltration. Mice deficient in CD4(+) T cells showed less tissue loss, while mice lacking CD8(+) T cells showed lesions comparable to those in immunocompetent mice. Mice deficient in both CD4(+) and CD8(+) T cells developed severe tissue loss similar to immunocompetent mice and this was associated with extensive infiltration of macrophages. The number of CD4(+) cells and macrophage/microglial cells, but not CD8(+) cells, infiltrating the hippocampal gyrus was correlated with the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive pyramidal neurons. These results suggest that CD4(+) T cells can promote progressive neuronal death and tissue injury, despite clearance of infectious virus. (C) 2003 Elsevier Science (USA). All rights reserved.