Study on demyelination of mice infected with coronavirus

研究了小鼠肝炎病毒（MHV）突变体JHMcc的神经致病性，该突变体来源于持续感染MHV- jhm的DBT细胞培养物。将10^6 PFU的JHMcc病毒接种于4周龄的ICR小鼠脑内或鼻内。脑内接种5天后，约20%的小鼠开始出现后肢瘫痪。脑和脊髓病毒滴度在感染后4 ~ 5 d达到峰值10^6PFU/0.2g，随后逐渐下降，接种后14 d无病毒获救。病理上，最显著的发现是脑干和脊髓白质有明显的空泡改变，脑膜和脑小血管周围有炎症细胞浸润，嗜神经细胞和胶质结节。即使在感染性病毒和病毒抗原消失后，这些变化在大小和数量上仍在继续发展。在鼻内感染后，病毒抗原似乎通过嗅觉系统出现，最终到达脑干和脊髓神经元。电镜分析显示，空泡改变是由于明显的髓鞘分裂和层间水肿，部分是由于神经鞘内空泡化。环磷酰胺治疗或裸鼠均不能预防。JHMcc病毒不会引起小鼠脱髓鞘，但会引起特征性的空泡改变，类似于艾滋病的空泡性脊髓病或HAM的脊髓变性。该病毒感染模型有助于阐明与某些病毒感染相关的空泡变性机制。

Neuropathogenicity of a mutant of mouse hepatitis virus (MHV), JHMcc which was derived from DBT cell cultures persistently infected with MHV-JHM was studied in mice. Four-week-old ICR mice were inoculated intracerebrally or intranasally with 10^6 PFU of JHMcc virus. Five days after intracerebral inoculation about 20% of mice began to develop hindlimb paralysis.The viral titers in the brain and spinal cord were 10^6PFU/0.2g ata peak 4 or 5 days after infection, then decreased gradually and no virus was rescued any more after 14 days postinoculation. Pathologically, the most remarkable finding was marked vacuolar changes in the brainstem and spinal cord white matter in addition to inflammatory cell infiltrations in the meninges and around the small vessels in the brain, neuronophagia and glial nodules. These changes progressed in size and number even after disapperance of infectious virus and viral antigens. After intranasal infection the viral antigens seemed to appear through the olfactory system and finally reached in the brainstem and spinal cord neurons. An electromicroscopic analysis revealed that the vacuolar changes weredue to marked myelin splitting and intralamellar edema and in part to intraneurite vacuolation. They could not be prevented with cyclofosphamide treatment or in nude mice. JHMcc virus dose not cause demyelination in mice, but characteristic vacuolar changes which resemble pathologically vacuolar myelopathy in AIDS or spinal cord degeneration in HAM. This JHMcc virus infection model could be useful to elucidate the mechanism of vacuolar degeneration associatedwith some viral infections.