SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements

Figures

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  Figure 1. Differential retrotranscriptome profiling of in vitro viral infection of lung adenocarcinoma cell lines (Calu-3, A549, and A549-ACE2). Volcano plots of differential retroelement expression induced by related human coronaviruses in Calu-3 cells (A–D), various respiratory virus infections in A549 cells (E–I), and SARS-CoV-2 infection of A549-ACE2 cells at different MOIs and pretreated with ruxolitinib kinase inhibitor (J–M).

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  Figure 2. Network analysis of gene and retroelement expression changes induced by various viral infections. (A) Selected gene clusters produced from the comparison of the transcriptomes of Calu-3 cells in 4 infection conditions (MOCK; SARS_Cov2; SARS; MERS). For each cluster, the scaled mean expression value (z score) for each gene in each group is plotted as a point. Box plots show the median expression z score (dark line) and the first and third quartiles (edges) of the cluster’s gene expression values in each condition. (B) Overrepresentation analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (left) and Gene Ontology (GO) terms (right) for selected Calu-3 clusters. Terms in the heatmap are shaded according to –log10(P), using the P value obtained from a hypergeometric test for each term’s overrepresentation in each cluster’s set of genes. Terms with P > 0.05 are not shaded. (C) Selected gene clusters from the comparison of the transcriptomes of A549 cells in 5 infection conditions (MOCK; SARS_Cov2; IAV; RSV; HPIV3). (D) KEGG and GO enrichment analysis results for selected A549 cell clusters. (E) Selected gene clusters from the comparison of the transcriptomes of…

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  Figure 3. ChIP-Seq analysis of SARS-CoV-2–induced differentially expressed TEs. (A) Heatmap summarizing the transcription factor (TF) occupancy over individual differentially expressed (DE) TE proviral loci in 14 human cell lines. This plot includes the distinct DE-TE loci that are occupied by at least 1 ChIP-Seq peak. Each row represents an individual DE-TE locus. Each column shows TF ChIP-Seq peak occupancy of a different cell line. Gray color denotes the absence, whereas dark red color denotes the presence of peaks in each locus. TFs are annotated on the top of the heatmap and shown in a legend on the right side. (B) Bar plot shows the number of DE-TE loci occupied by each ChIP-Seq in each cell line analyzed in A. The bars are shown in ascending order according to the number of enriched DE-TE loci. The ChIP-Seq shown in the box occupy at least half of the total DE-TE loci. (C) Heatmap shows the subsection of analysis in A while only including the attested and predicted pioneer TFs. The color scheme of the plot and legends is the same as in A. (D) This heatmap shows the subsection of analysis in A, including only the transcriptional- and enhancer-associated factors in A549 cells. The…

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  Figure 4. Differential retrotranscriptome profiling of RNA-Seq data from clinical samples from donors with COVID-19. Volcano plots of differentially expressed TEs from BALF samples from donors with COVID-19 compared with healthy donors separated by (A) HERVs and (B) LINE-1 elements. Volcano plots of differentially expressed TEs from PBMCs of patients with COVID-19 compared with healthy donors separated by (C) HERVs and (D) LINE-1 elements. (E) Upset plot of differentially expressed retroelement intersections across SARS-CoV-2 (COV2) infections of Calu-3 cells, A549 cells, A549-ACE2 cells, and BALF and PBMCs from clinical samples of patients with severe COVID-19.