Study on demyelination of mice infected with coronavirus

本文研究了小鼠肝炎病毒（MHV）突变株JHMcc的神经致病性。4周龄ICR小鼠脑内或鼻内接种10^6 PFU JHMcc病毒。脑内接种后5天约有20%的小鼠出现后肢瘫痪，脑和脊髓中病毒滴度在感染后4 ~ 5天达高峰，为10^6PFU/0.2g，随后逐渐下降，14天后无病毒再被拯救。病理学上，最显著的发现是脑干和脊髓白色物质中的明显空泡变化，以及脑膜和脑内小血管周围的炎性细胞浸润、神经元吞噬和神经胶质结节。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有进展。鼻内感染后，病毒抗原似乎通过嗅觉系统出现，并最终到达脑干和脊髓神经元。电镜分析表明，空泡变化是由于髓鞘分裂和层间水肿以及部分神经元内空泡化所致。环磷酰胺治疗或在裸鼠中不能预防它们。JHMcc病毒在小鼠中不引起脱髓鞘，但引起特征性空泡改变，其病理学上类似于AIDS中的空泡性脊髓病或HAM中的脊髓变性。这种JHMcc病毒感染模型可能有助于阐明某些病毒感染引起的空泡变性机制。

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.