Fig. 6: Associated functions and pathways of human genes responding to SARS-CoV-2 infection.

a Temporal expression changes of the human genes whose protein products were detected to interact with SARS-CoV-2 proteins⁵⁶ (brown) with ACE2 and TMPRSS2 highlighted in blue. For mRNA-seq (left), RPF-seq (middle), and QTI-seq (right) data, log₂(expression fold changes) for the genes at each time point were measured. Otherwise as in Fig. 5c. b Temporal expression changes of the host factors required for SARS-CoV-2 infection (brown), identified by CRISPR screening⁵⁷. Host factors whose targeting drugs were found in the Drug Gene Interaction database (DGIdb) are highlighted in magenta. The gray lines represent the expression changes of individual differentially expressed genes (DEGs) identified in Fig. 5. For mRNA-seq (left), RPF-seq (middle), and QTI-seq (right) data, log₂(expression fold changes) for the genes at each time point were measured. c Association between the magnitude of differential expression and the impact on SARS-CoV-2 infectivity for the host factors investigated in b. The x-axis represents the maximum of the absolute values of RPF-seq log₂(expression fold changes) across the time points. The y-axis represents the ranks of the CRISPR screening enrichment for the host factors⁵⁷. Spearman’s correlation ρ was measured between the two values, and the P value was obtained by using two-sided Student’s t test. Otherwise as in b. d Temporal expression changes of the type I and III interferon (IFN-α, β, ε, κ, λ, and ω) (green) and previously reported DEGs involved in type I interferon response⁵⁹ (brown). Otherwise as in a. e Temporal expression changes of the previously reported DEGs involved in cytokine and chemokine activities⁵⁹ (brown). Otherwise as in a. f Gene Ontology (GO) terms associated with DEGs identified from mRNA-seq (left) and RPF-seq (right) data are shown from 0 to 36 hpi. At each time point, statistical significance of the GO terms is visualized as a heat map, color-coded by −log₁₀(FDR-corrected q values). g DAVID KEGG pathways associated with DEGs identified from mRNA-seq (left) and RPF-seq (right) data are shown from 0 to 36 hpi. Association significance of each KEGG pathway with mRNA-seq data (left) and RPF-seq data (right) is shown. Otherwise as in f. h Expression levels of human miRNAs upon SARS-CoV-2 infection at each time point with upregulated (left) and downregulated (right) miRNAs highlighted. Expression levels of each miRNA were measured as RPM for each time point (see “Methods”) and displayed as log₁₀(RPM + 1). i Temporal expression changes of the genes reported to enhance (red) or suppress (blue) the translation initiation at non-AUG codons³³. Otherwise as in a. j Multiple sequence alignments for the 5′ leader region of betacoronaviruses. Two representative viruses from each lineage are displayed. See Supplementary Fig. 11i for multiple sequence alignments for a full list of betacoronaviruses.