SARS-CoV-2 variants evolve convergent strategies to remodel the host response

Publication
"SARS-CoV-2 variants evolve convergent strategies to remodel the host response" by Bouhaddou et al.

Abstract
SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host selective forces driving VOC evolution. We discovered VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with expression of viral innate immune antagonist proteins, including Orf6, N and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, though muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

Tables
RNA (tables 1), peptide (table 3, 6, 7), and protein (tables 4) counts and quantitative statistical comparisons (e.g. log2 fold changes and p-values; tables 2, 5, 8) between conditions, across both host and viral genes, during infection.
Table 1. Quantification of host RNA transcript counts in transcripts per million during infection, related to Figure 2.
Table 2. Differential host RNA expression analysis comparing conditions during infection, related to Figures 1 and 4.
Table 3. Quantification of host and viral proteins using abundance proteomics at the feature level, related to Figures 2 and 5.
Table 4. Quantification of host and viral proteins using abundance proteomics at the protein level, related to Figures 2 and 5.
Table 5. Differential host protein expression analysis comparing conditions during infection, related to Figures 1 and 4.
Table 6. Quantification of host and viral phosphorylated peptides using phosphoproteomics at the feature level, related to Figure 2.
Table 7. Quantification of host and viral phosphorylation sites using phosphoproteomics summarized at the site level, related to Figure 2.
Table 8. Differential host phosphorylation site intensity analysis comparing conditions during infection, related to Figures 1 and 4.

Supplemental Tables
Table S1. Consensus mutations in the VOCs from CoVariants.org, related to Figure 1.
Table S2. Viral RNA, protein, and phosphorylation site abundances during infection, including analysis comparing viral phosphorylated peptide intensities across VOCs, related to Figures 2 and 5.
Table S3. Affinity purification mass spectrometry (APMS) metadata and results, related to Figure 3.
Table S4. Integrative computational analysis metadata and results, related to Figure 4.