Symptoms from infection by SARS-CoV-2, the virus causing COVID-19, can range from mild to severe. As we know, severe COVID-19 results from an overreaction of the immune system, known as a cytokine storm. Cytokines are molecules acting as immune response mediators that orient how antiviral defenses should deploy. To understand how this overreaction is triggered, we infected mice and human cells with SARS-CoV-2 and examined how the virus modulates the immune response early in the infection.
Our results show that SARS-CoV-2 skews the immune response in favor of a pro-inflammatory reaction to the detriment of an effective antiviral defense. The induction of this pro-inflammatory response can be attributed in part to the non-structural protein 2 (Nsp2) of the virus that activates a key pathway involved in the expression of pro-inflammatory genes. As a result, the infected tissue is invaded by white blood cells, which further contributes to the inflammatory overreaction, ultimately leading to acute respiratory symptoms. Overall, our work helps better understand how SARS-CoV-2 infection leads to disease and provides information that could be of relevance for the development of effective therapeutic strategies.
Lacasse É, Gudimard L, Dubuc I, Gravel A, Allaeys I, Boilard É, Flamand L. SARS-CoV-2 Nsp2 Contributes to Inflammation by Activating NF-κB. Viruses. 2023 Jan 24;15(2):334. doi: https://doi.org/10.3390/v15020334. PMID: 36851549; PMCID: PMC9964531.