Fig. 5: Distinct transcriptional signatures are associated with early and late immune responses to SARS-CoV-2 infection.
a–g, RNA-seq analysis of the lung homogenates of naive K18-hACE2 mice and at 2, 4 and 7 dpi (two independent experiments; n = 4 for naive mice; n = 5 for 2 dpi; n = 6 for 4 dpi; n = 5 for 7 dpi). a, Principal component analysis was performed for 20 samples with the log2-transformed gene-level counts per million (log2[CPM]) data. PC, principal component. b, Volcano plots comparing differentially expressed genes from samples taken at day 2 versus day 0, day 4 versus day 0, and day 7 versus day 0. Red and blue indicate upregulated and downregulated genes, respectively, with a fold change > 2 and a false discovery rate (q value) < 0.05. Multiple comparisons were accounted for by calculation of a Benjamini–Hochberg false discovery rate-adjusted P value (that is, q value). Dashed horizontal lines mark a q value of 0.05 and dashed vertical lines indicate a log2[fold change] of 1 and −1. Each dot in the volcano plots represents a single gene. c, Venn diagram of overlapping genes identified in differential expression analysis when comparing the mock treatment with 2, 4 and 7 dpi. Numbers in parentheses under each comparison indicate the total number of significantly differential genes followed by the proportion of the total that are up- and downregulated. d, Gene Ontology (GO) enrichment analysis of biological process (BP) terms enriched in upregulated genes from comparisons of mice at 2, 4 and 7 dpi versus mock-infected mice. Terms were ranked by the false discovery rate (q value) and the top 20 are listed after eliminating redundant terms. Bars show the percentage of genes enriched. Red lines and data points show the −log10[q value]. NF-κB, nuclear factor-κB. e–g, Heat maps of significantly upregulated genes during SARS-CoV-2 infection enriched in the cytokine-mediated signaling pathway (e), type I IFN signaling pathway (f) and cellular response to IFN-γ (g), identified through Gene Ontology analysis. Genes shown in each pathway are the union of the differentially expressed genes from the three comparisons (2, 4 and 7 dpi versus mock infected). Columns represent samples and rows represent genes. Gene expression levels in the heat maps are z score–normalized values determined from log2[CPM] values. D, day.
