Fig. 3. Nucleocapsid shifts THP-1 macrophage-like cells from intracellular sensing to extracellular sensing.

(A and B) Transcription factor predictions of N-mediated gene up-regulation in TLR7/8 and TLR3 pathways. The 69 N–up-regulated genes after TLR7/8 stimulation and 140 N–up-regulated genes after TLR3 stimulation were analyzed for responsible transcription factors through TRRUST, a manually curated database of human and mouse transcriptional regulatory networks. The top 10 predicted transcription factors based on enrichment significance (FDR) are listed. The gradient colors correspond to combined enrichment scores. The size of the dots corresponds to the overlap ratio of the N–up-regulated genes in transcription factor–target genes in the database. The line segments exceeding −log₁₀(FDR) cutoff (red line, FDR = 0.05) shows significant enrichment. (C to E) Expression comparison of gene targets involved in multiple inflammatory pathways in parental THP-1 macrophage-like cells and Wuhan N–expressing THP-1 macrophage-like cells after different PRR stimulation. The log₂ fold changes of target genes of NF-κB and MAPK as well as proinflammatory transcription factors, AP-1 and EGR1, were extracted from the RNA-seq data and compared between parental THP-1 macrophage-like cells and Wuhan N–expressing THP-1 macrophage-like cells as bar graphs. The corresponding statistical significances of fold changes are indicated as asterisks: *P < 0.05; **P < 0.01; ***P < 0.001. Nonsignificant differences are not shown.