Type I interferon signaling induces a delayed antiproliferative response in respiratory epithelial cells during SARS-CoV-2 infection.
Juliana Bragazzi CunhaKyle LeixEmily J ShermanCarmen MirabelliTristan FrumCharles J ZhangAndrew A KennedyAdam S LauringAndrew W TaiJonathan Z SextonJason R SpenceChristiane E WobusBrian T EmmerPublished in: Journal of virology (2023)
The proliferation of respiratory epithelial cells is crucial to host recovery from acute lung injury caused by SARS-CoV-2 and other viral pathogens, but the molecular pathways that govern this process are poorly understood. We performed a high-throughput CRISPR screen that surprisingly revealed a detrimental effect of specific host response, type I interferon (IFN-I) signaling, on the fitness of SARS-CoV-2-infected Calu-3 cells. While IFN-I signaling has been previously associated with several potential downstream responses, we found this effect to be primarily mediated by an inhibition of Calu-3 cellular proliferation after the early peak of SARS-CoV-2-induced cell death. Our findings provide a plausible mechanism for how sustained IFN-I signaling during SARS-CoV-2 infection might worsen lung pathology by blocking the regeneration of the alveolar epithelium from progenitor cells.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- dendritic cells
- high throughput
- cell death
- immune response
- signaling pathway
- stem cells
- cell cycle arrest
- induced apoptosis
- physical activity
- lipopolysaccharide induced
- coronavirus disease
- dna methylation
- oxidative stress
- drug induced
- genome wide
- inflammatory response
- pi k akt
- single molecule
- endoplasmic reticulum stress
- risk assessment
- antimicrobial resistance
- cell proliferation
- wound healing