生物
重编程
细胞生物学
免疫系统
病毒
甲型流感病毒
焊剂(冶金)
病毒学
微生物学
细胞
免疫学
生物化学
材料科学
冶金
作者
Qi Wen Teo,Ho Him Wong,Tiaan Heunis,Viktoriya Stancheva,Asmaa Hachim,Huibin Lv,Lewis Siu,Julian Ho,Yun Lan,Chris Ka Pun Mok,Rachel Ulferts,Sumana Sanyal
标识
DOI:10.1016/j.devcel.2023.08.013
摘要
Reprogramming lipid metabolic pathways is a critical feature of activating immune responses to infection. However, how these reconfigurations occur is poorly understood. Our previous screen to identify cellular deubiquitylases (DUBs) activated during influenza virus infection revealed Usp25 as a prominent hit. Here, we show that Usp25-deleted human lung epithelial A549 cells display a >10-fold increase in pathogenic influenza virus production, which was rescued upon reconstitution with the wild type but not the catalytically deficient (C178S) variant. Proteomic analysis of Usp25 interactors revealed a strong association with Erlin1/2, which we confirmed as its substrate. Newly synthesized Erlin1/2 were degraded in Usp25-/- or Usp25C178S cells, activating Srebp2, with increased cholesterol flux and attenuated TLR3-dependent responses. Our study therefore defines the function of a deubiquitylase that serves to restrict a range of viruses by reprogramming lipid biosynthetic flux to install appropriate inflammatory responses.
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