USP18 promotes innate immune responses and apoptosis in influenza A virus-infected A549 cells via cGAS-STING pathway.

Influenza A virus (IAV) can infect respiratory epithelial cells where it replicates, triggers cellular innate immune responses, and even induces cell apoptosis. Ubiquitin-specific peptidase 18 (USP18) was reported to be associated with IAV replication and immune response homeostasis. Therefore, this study aimed to investigate the role of USP18 in IAV-infected lung epithelial cells. The cell viability was determined by the CCK-8 method. Viral titers were quantified by standard plaque assay. Innate immune response-associated cytokines were detected by RT-qPCR and ELISA and cell apoptosis was assessed by flow cytometry. The results showed that overexpression of USP18 promoted viral replication, innate immune factor secretion and apoptosis in IAV-infected A549 cells. Mechanistically, USP18 reduced cGAS degradation by decreasing its K48-linked ubiquitination to promote IAV-induced cGAS-STING pathway activation. In conclusion, USP18 is a pathological mediator of IAV in lung epithelial cells. [Display omitted] • IAV promote their own replication by increasing USP18 levels. • USP18 mediates innate immune responses in IAV-infected lung epithelial cells. • USP18 mediates apoptosis in IAV-infected lung epithelial cells. • USP18 reduces cGAS degradation by decreasing its ubiquitination to promote cGAS-STING pathway activation. [ABSTRACT FROM AUTHOR]