TRIM45 restricts influenza virus infection through modulating the chaperone-mediated autophagic degradation of viral PB2 protein.

ABSTRACT: The host defense system employs elaborate mechanisms to combat invading viruses. Here, we demonstrate that tripartite motif containing 45 (TRIM45) restricts the replication of different subtypes of influenza virus. TRIM45 interacted with and reduced the level of viral polymerase basic protein 2 (PB2). PB2 associated with heat shock cognate protein 70 (HSC70) and lysosomal-associated membrane protein type 2A (LAMP-2A), and was directed for lysosomal degradation via chaperone-mediated autophagy (CMA). TRIM45 promoted LAMP-2A expression and enhanced PB2/LAMP-2A binding, thereby facilitating CMA-dependent PB2 degradation. Mechanistically, TRIM45 employed its E3 ubiquitin ligase activity to mediate the K48-linked polyubiquitination and proteasomal degradation of Ca2 + -dependent cysteine protea

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12578348 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature