MARCH6 suppresses Tembusu virus replication by targeting viral NS5 protein for TOLLIP-mediated selective autophagic degradation.

ABSTRACT: The E3 ligase membrane-associated RING finger 6 (MARCH6) plays a pivotal role in various cellular processes; however, its role in viral defense remains largely unexplored. In this study, we have elucidated a novel antiviral mechanism of avian MARCH6 against duck Tembusu virus (TMUV), revealing a previously uncharacterized host defense strategy. Notably, MARCH6 expression was significantly upregulated during TMUV infection in several duck cell lines, suggesting a conserved cellular response. Functional analyses revealed that overexpression of MARCH6 effectively suppressed TMUV replication, whereas its knockdown markedly enhanced viral replication. Mechanistically, MARCH6 directly interacts with the viral non-structural protein 5 (NS5), mediating its targeted degradation through an unprecede

SUBMITTER: Zhou P 

PROVIDER: S-EPMC12282148 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature