The E3 ubiquitin ligase FBXL18 stabilizes BST2 to promote inflammation in RABV-infected astrocytes

ABSTRACT: Lethal encephalitis caused by rabies virus (RABV) in mammals is known to be associated with the production of several pro-inflammatory cytokines, but the mechanism of such induction remains unclear. In this study, we found that RABV infects astrocytes which is the most abundant glial cell population and the dominant source of inflammatory factors in the central nervous system (CNS). A screen identified the E3 ubiquitin ligase FBXL18 as a critical factor responsible for RABV-induced inflammation. Mechanistically, infection by RABV up-regulates FBXL18, which induces K11-type ubiquitination of BST2 on Lys109 and Lys110, two residues that are also targeted by K33-type ubiquitination for degradation. FBXL18-mediated ubiquitination stabilizes BST2, leading to hyperphosphorylation of IκBα and excessive NF-κB activation. Knockdown of FBXL18 effectively inhibits IL-6 production and RABV replication. Our findings suggest that targeting FBXL18 is a potentially effective strategy for rabies treatment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Liu Yan  

LAB HEAD: Yan Liu

PROVIDER: PXD058558 | Pride | 2025-12-29

REPOSITORIES: Pride