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

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

Publication date: Sep 19, 2023

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 that 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 the 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, although muted in BA. 4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

Concepts Keywords
Nuclear innate immunity
Proteins protein-protein interactions
Remodel proteomics
Unbiased SARS-CoV-2
Viral systems biology
virus-host interactions


Type Source Name
disease IDO host
disease MESH COVID-19 pandemic

Original Article

(Visited 1 times, 1 visits today)