Study on demyelination of mice infected with coronavirus

研究了小鼠肝炎病毒(MHV)突变株JHMcc对小鼠神经致病性的影响。用JHMcc病毒10^6pfu经脑内或鼻腔接种四周龄ICR小鼠。脑内接种病毒后5d，约有20%的小鼠出现后肢瘫痪，感染后4~5d，脑和脊髓中病毒滴度最高，为10.6pfu/0.2g，14d后逐渐下降，无病毒存活。病理上，最显著的改变是脑干和脊髓白质明显的空泡改变，脑膜和脑内小血管周围的炎性细胞浸润，吞神经节和神经胶质结节。即使在传染性病毒和病毒抗原消失后，这些变化在大小和数量上仍有进展。在鼻腔感染后，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。电子显微镜分析表明，空泡的改变是由于显着的髓鞘裂解和板层内水肿，部分是由于神经细胞内的空泡化。它们不能用环磷酰胺治疗或在裸鼠体内预防。JHMcc病毒不会引起小鼠脱髓鞘，而是典型的空泡样改变，类似于艾滋病的空泡性脊髓病或HAM的脊髓变性。该JHMcc病毒感染模型可用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.