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. Author manuscript; available in PMC: 2022 Mar 23.
Published in final edited form as: Nat Immunol. 2021 Sep 23;22(10):1280–1293. doi: 10.1038/s41590-021-01012-1

Figure 8. Viral infection after CVI leads to chronic interferon signaling and a failure to recover cognitive-motor function.

Figure 8.

a-g. RNA sequencing analysis of gene expression in the cerebral cortex of uninjured mice (Ctrl) as well as uninfected (CVI) and d4 LCMV-infected B6 mice (CVI LCMV) at day 10 post-CVI (n=4 per group). a. A Pearson correlation-based clustered heat map shows the unique union of genes deemed to have a significant difference of expression between at least two classes. b. Covariance-based PCA scatterplot shows separate clustering of the different groups. Each dot represents individual mouse. c, d. Bar graphs demonstrate the p-value and upregulated gene ratio of 10 enriched pathways with the lowest enrichment p-value for CVI vs Ctrl mice (c) and CVI LCMV vs Ctrl mice mice (d). e, f. Ingenuity software based canonical pathway view of interferon signaling related genes in CVI vs Ctrl mice (e) and CVI LCMV vs Ctrl mice (f). Upregulated genes are shown in shades of green. g. A custom network view of all genes directly (solid lines) and indirectly (dotted lines) associated with interferon (Ifn) in CVI LCMV vs CVI mice. Upregulated genes are shown in shades of green and downregulated genes in shades of red. Source data and Ingenuity analysis analysis for a-g in Supplementary Tables 2–4. h, i. Dot plots show quantification of cognitive-motor function by Y-maze at day 20 after CVI in uninfected (Ctrl) and d4 LCMV-infected (LCMV), B6 and IFNAR−/− mice. The number of gates entered (h) and the triplicate ratio (i) are plotted. Cumulative data from four independent experiments. Each symbol represents an individual mouse and asterisks denote statistical significance. Data are represented as mean ± SD. (Sham n=10, Ctrl B6 n=24, LCMV B6 28, Ctrl IFNAR−/− 9, LCMV IFNAR−/− 16; **P<0.01, ***P<0.001, ****P<0.0001; Two-way ANOVA/ Holm-Sidak test ). Source data for h, i in Source Data Fig. 8. Statistical analysis in Supplementary Table 5.