Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, primarily oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), survive the acute MHV infection, are associated with regions of demyelination, and persist in the central nervous system (CNS) for at least 150 d. These surviving OLs express major histocompatibility complex (MHC) class I and other genes associated with an inflammatory response. Notably, the extent of inflammatory cell infiltration was variable, dependent on anatomic location within the CNS, and without obvious correlation with numbers of surviving cells. We detected more demyelination in regions with larger numbers of T cells and microglia/macrophages compared to those with fewer infiltrating cells. Conversely, in regions with less inflammation, these previously infected OLs more rapidly extended processes, consistent with normal myelinating function. Together, these results show that OLs are inducers as well as targets of the host immune response and demonstrate how a CNS infection, even after resolution, can induce prolonged inflammatory changes with CNS region-dependent impairment in remyelination.

小鼠肝炎病毒（MHV）是一种冠状病毒，其嗜神经毒株可引起急性和慢性脱髓鞘性脑脊髓炎，与人类疾病多发性硬化症相似。在这里，使用谱系追踪系统，我们发现一些细胞，主要是少突胶质细胞 (OL) 和少突胶质细胞前体细胞 (OPC)，在急性 MHV 感染中存活下来，与脱髓鞘区域相关，并持续存在于中枢神经系统 (CNS) 中。 ）至少150天。这些幸存的 OL 表达 I 类主要组织相容性复合体 (MHC) 和其他与炎症反应相关的基因。值得注意的是，炎症细胞浸润的程度是可变的，取决于中枢神经系统内的解剖位置，并且与存活细胞的数量没有明显的相关性。与浸润细胞较少的区域相比，我们在 T 细胞和小胶质细胞/巨噬细胞数量较多的区域检测到更多的脱髓鞘。相反，在炎症较少的区域，这些先前感染的 OL 会更快地延长过程，这与正常的髓鞘形成功能一致。总之，这些结果表明，OLs 是宿主免疫反应的诱导剂和靶标，并证明中枢神经系统感染即使在消退后，也可以诱导长期炎症变化，并导致中枢神经系统区域依赖性髓鞘再生损伤。