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

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 se...

Full description

Saved in:

Bibliographic Details
Published in:	Communications biology 2022-01, Vol.5 (1), p.45-45, Article 45
Main Authors:	Neufeldt, Christopher J, Cerikan, Berati, Cortese, Mirko, Frankish, Jamie, Lee, Ji-Young, Plociennikowska, Agnieszka, Heigwer, Florian, Prasad, Vibhu, Joecks, Sebastian, Burkart, Sandy S, Zander, David Y, Subramanian, Baskaran, Gimi, Rayomand, Padmanabhan, Seetharamaiyer, Iyer, Radhakrishnan, Gendarme, Mathieu, El Debs, Bachir, Halama, Niels, Merle, Uta, Boutros, Michael, Binder, Marco, Bartenschlager, Ralf
Format:	Article
Language:	eng
Subjects:	Antiviral agents Biology COVID-19 - metabolism COVID-19 - virology Cytokine Release Syndrome Cytokines Drug delivery Epithelial cells Humans Immune response Immunosuppressive agents Inflammation Inflammation Mediators - metabolism Interferon regulatory factor 3 Membrane Proteins - metabolism NF-kappa B - metabolism NF-κB protein Nuclear transport Nucleotidyltransferases - metabolism Pandemics SARS-CoV-2 - isolation & purification Severe acute respiratory syndrome coronavirus 2 Signal Transduction Transcription
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	2399-3642 2399-3642