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Experimental infection of mice with Theiler's murine encephalomyelitis virus (TMEV) causes diverse neurologic diseases, including TMEV\u2010induced demyelinating disease (TMEV\u2010IDD), depending on the used mouse strain. The aim of the present study was to compare initial transcriptomic changes occurring in the brain of TMEV\u2010infected SJL (TMEV\u2010IDD susceptible) and C57BL\/6 (TMEV\u2010IDD resistant) mice. Animals were infected with TMEV and sacrificed 4, 7, or 14\u00a0days post infection. RNA was isolated from brain tissue and analyzed by whole\u2010transcriptome sequencing. Selected differences were confirmed on a protein level by immunohistochemistry. In mock\u2010infected SJL and C57BL\/6\u00a0mice, &gt;200 differentially expressed genes (DEGs) were detected. Following TMEV\u2010infection, the number of DEGs increased to &gt;700. Infected C57BL\/6\u00a0mice 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\u00a0mice, which presumably facilitates the induction of chronic demyelinating disease. In addition, elevated expression of several genes associated with immunomodulatory or \u2013suppressive 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.<\/jats:p>","DOI":"10.1111\/bpa.13000","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T05:37:06Z","timestamp":1625636226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptome analysis following neurotropic virus infection reveals faulty innate immunity and delayed antigen presentation in mice susceptible to virus\u2010induced demyelination"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-7366","authenticated-orcid":false,"given":"Malgorzata","family":"Ciurkiewicz","sequence":"first","affiliation":[{"name":"Department of Pathology University of Veterinary Medicine Hannover Hannover 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