Viral infections of the central nervous system cause acute or delayed neuropathology and clinical consequences ranging from asymptomatic courses to chronic, debilitating diseases. The outcome of viral encephalitis is partially determined by genetically programed immune response patterns of the host. Experimental infection of mice with Theiler's murine encephalomyelitis virus (TMEV) causes diverse neurologic diseases, including TMEV-induced demyelinating disease (TMEV-IDD), depending on the used mouse strain. The aim of the present study was to compare initial transcriptomic changes occurring in the brain of TMEV-infected SJL (TMEV-IDD susceptible) and C57BL/6 (TMEV-IDD resistant) mice. Animals were infected with TMEV and sacrificed 4, 7, or 14 days post infection. RNA was isolated from brain tissue and analyzed by whole-transcriptome sequencing. Selected differences were confirmed on a protein level by immunohistochemistry. In mock-infected SJL and C57BL/6 mice, >200 differentially expressed genes (DEGs) were detected. Following TMEV-infection, the number of DEGs increased to >700. Infected C57BL/6 mice showed a higher expression of transcripts related to antigen presentation via major histocompatibility complex (MHC) I, innate antiviral immune responses and cytotoxicity, compared with infected SJL animals. Expression of many of those genes was weaker or delayed in SJL mice, associated with a failure of viral clearance in this mouse strain. SJL mice showed prolonged elevation of MHC II and chemotactic genes compared with C57BL/6 mice, which presumably facilitates the induction of chronic demyelinating disease. In addition, elevated expression of several genes associated with immunomodulatory or –suppressive functions was observed in SJL mice. The exploratory study confirms previous observations in the model and provides an extensive list of new immunologic parameters potentially contributing to different outcomes of viral encephalitis in two mouse strains.

中文翻译：

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嗜神经病毒感染后的转录组分析揭示了易受病毒诱导的脱髓鞘影响的小鼠的先天免疫缺陷和抗原呈递延迟

中枢神经系统的病毒感染会导致急性或迟发性神经病理学和临床后果，从无症状病程到慢性、使人衰弱的疾病不等。病毒性脑炎的结果部分取决于宿主的基因程序免疫反应模式。Theiler 鼠脑脊髓炎病毒 (TMEV) 对小鼠的实验性感染会导致多种神经系统疾病，包括 TMEV 诱发的脱髓鞘疾病 (TMEV-IDD)，具体取决于所使用的小鼠品系。本研究的目的是比较 TMEV 感染的 SJL（TMEV-IDD 易感）和 C57BL/6（TMEV-IDD 抗性）小鼠大脑中发生的初始转录组变化。用 TMEV 感染动物并在感染后 4、7 或 14 天处死。从脑组织中分离 RNA 并通过全转录组测序进行分析。通过免疫组织化学在蛋白质水平上确认了选定的差异。在模拟感染的 SJL 和 C57BL/6 小鼠中，检测到 >200 个差异表达基因 (DEG)。TMEV 感染后，DEG 的数量增加到 > 700。与受感染的 SJL 动物相比，受感染的 C57BL/6 小鼠通过主要组织相容性复合物 (MHC) I、先天抗病毒免疫反应和细胞毒性表现出与抗原呈递相关的转录物的更高表达。在 SJL 小鼠中，许多这些基因的表达较弱或延迟，这与该小鼠品系中病毒清除失败有关。与 C57BL/6 小鼠相比，SJL 小鼠的 MHC II 和趋化基因水平升高，这可能有助于诱发慢性脱髓鞘疾病。此外，在 SJL 小鼠中观察到与免疫调节或抑制功能相关的几个基因的表达升高。这项探索性研究证实了模型中先前的观察结果，并提供了一份广泛的新免疫学参数列表，这些参数可能导致两种小鼠病毒性脑炎的不同结果。