SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB

Abstract

SARS-CoV-2 is a novel virus that has rapidly spread, causing a global pandemic. In the majority of infected patients, SARS-CoV-2 leads to mild disease; however, in a significant proportion of infections, individuals develop severe symptoms that can lead to long-lasting lung damage or death. These severe cases are often associated with high levels of pro-inflammatory cytokines and low antiviral responses, which can cause systemic complications. Here, we have evaluated transcriptional and cytokine secretion profiles and detected a distinct upregulation of inflammatory cytokines in infected cell cultures and samples taken from infected patients. Building on these observations, we found a specific activation of NF-κB and a block of IRF3 nuclear translocation in SARS-CoV-2 infected cells. This NF-κB response was mediated by cGAS-STING activation and could be attenuated through several STING-targeting drugs. Our results show that SARS-CoV-2 directs a cGAS-STING mediated, NF-κB-driven inflammatory immune response in human epithelial cells that likely contributes to inflammatory responses seen in patients and could be therapeutically targeted to suppress severe disease symptoms.

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Cited by papers we hold 6

• The cGAS–STING pathway drives type I IFN immunopathology in COVID-19 · 2022
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• Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells? · 2021
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• SARS‐CoV‐2 sensing by RIG‐I and MDA5 links epithelial infection to macrophage inflammation · 2021
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• Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2 · 2021
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• The RNA sensor MDA5 detects SARS-CoV-2 infection · 2021
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• NF-κB Pathway as a Potential Target for Treatment of Critical Stage COVID-19 Patients · 2020
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