TRIM23 prevents adenovirus replication by p62-mediated selective autophagic degradation of viral E1A protein

Abstract

The E3 ubiquitin ligase TRIM23 is involved in diverse cellular processes, however, its function in antiviral defense against adenovirus remains unclear. Here, we identify a novel mechanism by which TRIM23 restricts human adenovirus type 5 (HAdV-C5) replication. TRIM23 expression was upregulated upon HAdV-C5 infection, and functional studies showed that its overexpression inhibited viral replication, while knockdown enhanced it. Mechanistically, TRIM23 interacts with the viral E1A protein and promotes its degradation through a mechanism dependent of its canonical E3 ligase activity. Moreover, TRIM23 recruits the selective autophagy receptor p62 promotes E1A degradation in a E1A ubiquitination-independent manner. Our results unveil a novel host defense pathway-the TRIM23-E1A-p62 axis-that highlights the role of selective autophagy in antiviral immunity.