Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection.

ABSTRACT: 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 Usp25^C178S cells, activating Srebp2, with

SUBMITTER: Teo QW 

PROVIDER: S-EPMC10914638 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature