Retrovirus-induced spongiform myeloencephalopathy in mice: regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons.

The Cas-Br-E murine leukemia virus (MuLV) induces a spongiform myeloencephalopathy resulting in a progressive hindlimb paralysis. We have used in situ hybridization with a Cas-Br-E MuLV-specific probe to study viral expression in the central nervous system. Infected cells were concentrated in regions where spongiform lesions and gliosis are detected (lumbosacral spinal cord, brainstem, deep cerebellar regions), suggesting a causative link between the level of virus expression and the degree of pathological changes in this disease. However, viral expression was not in itself sufficient to cause disease, since significant viral expression was observed in regions that did not exhibit pathological changes (cerebellar cortex, hippocampus, corpus callosum, peripheral nervous system). In both diseased and nondiseased regions, endothelial and glial cells were identified as the main target cells. Neurons in diseased regions did not show viral expression. The regional distribution of the spongiform changes appears to be laid down very early following infection, since expression could be detected at 10 days postinfection in regions that become diseased. These results indicate that nonneuronal cells have distinct properties in various regions of the central nervous system and suggest an indirect mechanism of neuronal loss consequent to viral expression in nonneuronal cells. IMAGES:

Cas-Br-E小鼠白血病病毒（murine leukemia virus, MuLV）可诱发海绵状脑脊髓病，引发进行性后肢麻痹。本研究采用针对Cas-Br-E MuLV的特异性探针开展原位杂交（in situ hybridization）实验，以探究该病毒在中枢神经系统（central nervous system）中的表达特征。受感染的细胞集中在存在海绵状病灶与胶质增生的区域（腰骶段脊髓、脑干、小脑深部区域），这提示该疾病中病毒表达水平与病理改变程度存在因果关联。然而，病毒表达本身并不足以引发疾病：在未出现病理改变的区域（小脑皮层、海马体、胼胝体、外周神经系统）同样可检测到显著的病毒表达。无论病变区域还是非病变区域，内皮细胞与胶质细胞均被鉴定为主要的靶细胞；病变区域内的神经元则未检测到病毒表达。海绵状病变的区域分布似乎在感染后极早期即已确定，因为在感染后10天即可在后续发生病变的区域中检测到病毒表达。上述结果表明，中枢神经系统不同区域的非神经元细胞具有独特的生物学特性，并提示非神经元细胞中的病毒表达可通过间接机制导致神经元丢失。IMAGES: 图像：