Authors
Jian Du, Chunwei Li, Jiyuan Luo, Huizhi Zhang, Jinyan Zhang, Suya Wang, Huanchun Chen, Hongli Xu, Xiangmin Li, Ping Qian
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e76122. Jun 18, 2026. Epub Jun 18, 2026.
Abstract
Japanese encephalitis virus (JEV) is a neurotropic flavivirus that causes a substantial threat to human health and livestock; however, the epitranscriptomic mechanisms that support its replication remain poorly defined. Here, we identify a proviral host factor C2H2 zinc-finger protein ZNF33B that promotes JEV infection through coupling N6-methyladenosine (m6A) RNA modification to autophagy regulation. Mechanistically, ZNF33B recruits METTL14 to stabilize the METTL3-METTL14 methyltransferase complex, thereby increasing global m6A deposition. Multi-omics analyses reveal that ZNF33B selectively binds m6A-modified sites within the antiviral transcript Trim25 (c.1567 and c.1669 bp) to accelerate its decay. We further demonstrate that TRIM25 functions as an E3 ubiquitin ligase that catalyzes K48-linked ubiquitination of ATG7 at lysines 389 and 423, leading to its proteasomal degradation and ultimately suppressing autophagic flux. In contrast, ZNF33B-mediated Trim25 degradation counteracts its inhibitory effect on autophagy, creating a favorable environment for viral replication. In vivo, adeno-associated virus (AAV)-mediated ZNF33B delivery increases mouse brain m6A levels, decreases TRIM25 expression, elevates ATG7 abundance, exacerbates JEV-induced neuropathology, and accelerates mouse mortality. Together, these findings reveal a previously uncharacterized ZNF33B-m6A-TRIM25-autophagy axis that JEV hijacks to evade host antiviral responses, providing new insights into flaviviral pathogenesis and potential therapeutic targets.
PMID:
42314059
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 2
- Comments 0