Jackson A C, Moench T R, Trapp B D, Griffin D E
Department of Neurology, Johns Hopkins University, Baltimore, Maryland.
Lab Invest. 1988 May;58(5):503-9.
Neuroadapted Sindbis virus (NSV) was selected by serial passage of wild-type Sindbis virus (SV) in mouse brain. After intracerebral inoculation of weanling mice, NSV causes a severe encephalomyelitis with hindlimb paralysis and high mortality; SV causes nonfatal mild disease. In order to determine the biologic basis of neurovirulence in vivo, these viral infections have been compared by using infectivity assays, light and electron microscopy, in situ hybridization, immunohistochemistry, and double-labeling for neural cell markers and viral RNA. More infectious virus is present in the central nervous system during NSV than during SV infection. After intracerebral inoculation, both viruses enter the central nervous system via the ependyma and spread to gray matter areas, including the ventral horns of the spinal cord. Their cellular targets are not different, and neuronal infection is prominent. NSV infects more neurons, and causes more severe injury than SV. In NSV infection, there is marked swelling of lumbar and thoracic neurons and their processes in the ventral horns. Relatively mild changes are detected in SV infection only by electron microscopy. Neuroadaptation likely occurs by increasing the efficiency of viral replication in neurons, rather than by a fundamental change in the cellular tropism or the topography of the infection in the central nervous system.
神经适应型辛德毕斯病毒（NSV）是通过野生型辛德毕斯病毒（SV）在小鼠脑内连续传代筛选出来的。给断奶小鼠脑内接种后，NSV会引发严重的脑脊髓炎，伴有后肢麻痹和高死亡率；而SV引发的是不致命的轻度疾病。为了确定体内神经毒力的生物学基础，通过感染性测定、光学和电子显微镜检查、原位杂交、免疫组织化学以及对神经细胞标记物和病毒RNA进行双重标记等方法对这些病毒感染进行了比较。在NSV感染期间，中枢神经系统中存在的感染性病毒比SV感染期间更多。脑内接种后，两种病毒均通过室管膜进入中枢神经系统，并扩散至灰质区域，包括脊髓腹角。它们的细胞靶点并无差异，且神经元感染较为突出。NSV感染的神经元更多，对神经元造成的损伤也比SV更严重。在NSV感染中，脊髓腹角的腰段和胸段神经元及其突起明显肿胀。仅通过电子显微镜检查在SV感染中检测到相对轻微的变化。神经适应可能是通过提高病毒在神经元中的复制效率而发生的，而不是通过细胞嗜性或中枢神经系统感染的拓扑结构发生根本性改变。
