Wang Binbin, Xia Hongjie, Peng Bi-Hung, Choi Eun-Jin, Tian Bing, Xie Xuping, Makino Shinji, Bao Xiaoyong, Shi Pei-Yong, Menachery Vineet, Wang Tian
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, TX, USA.
Antiviral Res. 2025 Jan;233:106059. doi: 10.1016/j.antiviral.2024.106059. Epub 2024 Dec 15.
Enhanced expression of Pellino-1 (Peli1), a ubiquitin ligase is known to be associated with COVID-19 susceptibility. The underlying mechanisms are not known. Here, we report that mice deficient in Peli1 (Peli1) had reduced viral load and attenuated inflammatory immune responses and tissue damage in the lung following SARS-CoV-2 infection. Overexpressing Peli1 in 293 T cells increased SARS-CoV-2 infection via promoting virus replication and transcription, without affecting virus attachment and entry into the cells. Smaducin-6 treatment which is known to disrupt Peli1-mediated NF-KB activation, attenuated inflammatory immune responses in human lung epithelial cells as well as in the lung of K18-hACE2 mice following SARS-CoV-2 infection, though it had minimal effects on SARS-CoV-2 infection in human nasal epithelial cells. Overall, our findings suggest that Peli1 contributes to SARS-CoV-2 pathogenesis by promoting virus replication and positively regulating virus-induced inflammatory responses in lung epithelial cells. Peli1 is a therapeutic target to control SARS-CoV-2 -induced disease severity.
泛素连接酶Pellino-1（Peli1）的表达增强已知与新冠病毒易感性相关。其潜在机制尚不清楚。在此，我们报告，Peli1基因缺失的小鼠在感染新冠病毒后，肺部病毒载量降低，炎症免疫反应和组织损伤减轻。在293 T细胞中过表达Peli1通过促进病毒复制和转录增加了新冠病毒感染，而不影响病毒附着和进入细胞。已知Smaducin-6处理可破坏Peli1介导的NF-κB激活，在新冠病毒感染后，它减轻了人肺上皮细胞以及K18-hACE2小鼠肺部的炎症免疫反应，尽管它对人鼻上皮细胞中的新冠病毒感染影响极小。总体而言，我们的研究结果表明，Peli1通过促进病毒复制和正向调节肺上皮细胞中病毒诱导的炎症反应，促进了新冠病毒的发病机制。Peli1是控制新冠病毒所致疾病严重程度的治疗靶点。
