FHL2 Inhibits SARS-CoV-2 Replication by Enhancing IFN-β Expression through Regulating IRF-3

• Published in: International journal of molecular sciences Vol. 25; no. 1; p. 353
• Main Authors: Xu, Zhiqiang, Tian, Mingyao, Tan, Qihan, Hao, Pengfei, Gao, Zihan, Li, Chang, Jin, Ningyi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.12.2023; MDPI
• Subjects: FHL2; IFN-β; infection; Infections; IRF-3; Kinases; Phosphorylation; Protein expression; Proteins; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signal transduction; Tumor necrosis factor-TNF; Viruses; FHL2; IRF-3; SARS-CoV-2; infection; IFN-β
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25010353

SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with exhibiting a notable inhibitory impact on SARS-CoV-2 replication. , acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and remains unclear. In this study, we report for the first time that SARS-CoV-2 infection in Caco2 cells results in the upregulation of expression, while the virus's N proteins can enhance expression. Notably, the knockdown of significantly amplifies SARS-CoV-2 replication in vitro. Conversely, the overexpression of leads to a marked reduction in SARS-CoV-2 replication, with the antiviral property of being independent of the cell or virus type. Subsequent experiments reveal that supports transcription by upregulating the expression and phosphorylation of IRF-3, thereby impeding SARS-CoV-2 replication in cells. These findings highlight as a potential antiviral target for treating SARS-CoV-2 infections.