GSE159226
Transcriptome analysis of initial cerebral responses following neurotropic virus infection reveals faulty innate immunity and delayed antigen presentation in mice susceptible to virus-induced demyelination
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 programmed 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 intracerebrally with TMEV and sacrificed 4, 7 or 14 days post infection (dpi). Control animals of both strains were inoculated with vehicle only and sacrificed at 7 dpi. 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 mice 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 MHCI I, innate antiviral immune responses and cytotoxicity, compared to infected SJL animals. Many of those genes were also upregulated in SJL mice upon infection, but the response was weaker or delayed, which could be responsible for failure of viral clearance in this mouse strain. SJL mice showed prolonged elevation of MHC II and chemotactic genes, compared to 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 immunologic parameters potentially contributing to different outcomes of viral encephalitis in two mouse strains. Overall design: Whole transcriptome sequencing of brain tissue derived from SJL and C57BL/6 mice following mock- or TMEV-infection.