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 establish that the laboratory strain CVS-11 infects astrocytes which are the most abundant glial cell population and the dominant source of inflammatory factors in the central nervous system (CNS). A screen identifies the E3 ubiquitin ligase FBXL18 as a critical factor responsible for RABV-induced inflammation. Mechanistically, infection by RABV upregulates FBXL18, which induces K11-type ubiquitination of BST2 on Lys₁₀₉ and Lys₁₁₀, two residues that are also ubiquitinated for degradation via K33-type ubiquitination by a yet unknown E3 ligase. FBXL18-media

SUBMITTER: Wang J 

PROVIDER: S-EPMC12722208 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature