Department of Infectious Diseases, Xi'an Children's Hospital, Xi'an, 710002, Shaanxi, China.
Department of Infectious Diseases, Xi'an Children's Hospital, Xi'an, 710002, Shaanxi, China.
Virology. 2023 Aug;585:240-247. doi: 10.1016/j.virol.2023.06.012. Epub 2023 Jun 30.
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.
甲型流感病毒（IAV）可感染呼吸道上皮细胞并在其中复制，引发细胞固有免疫反应，甚至诱导细胞凋亡。泛素特异性肽酶 18（USP18）被报道与 IAV 复制和免疫反应稳态有关。因此，本研究旨在探讨 USP18 在 IAV 感染的肺上皮细胞中的作用。通过 CCK-8 法测定细胞活力。通过标准噬斑法定量病毒滴度。通过 RT-qPCR 和 ELISA 检测固有免疫反应相关细胞因子，通过流式细胞术评估细胞凋亡。结果表明，USP18 的过表达促进了 IAV 感染的 A549 细胞中的病毒复制、固有免疫因子分泌和细胞凋亡。机制上，USP18 通过减少其 K48 连接的泛素化来降低 cGAS 的降解，从而促进 IAV 诱导的 cGAS-STING 通路激活。总之，USP18 是肺上皮细胞中 IAV 的病理性介质。
