TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism

Int J Mol Sci. 2024 Apr 23;25(9):4616. doi: 10.3390/ijms25094616.

Abstract

Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.

Keywords: E3 ubiquitin ligase; TRIM44; autophagy; rabies virus; replication.

MeSH terms

  • Animals
  • Autophagy* / genetics
  • Cell Line, Tumor
  • Host-Pathogen Interactions
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Rabies / metabolism
  • Rabies / virology
  • Rabies virus* / genetics
  • Tripartite Motif Proteins* / genetics
  • Tripartite Motif Proteins* / metabolism
  • Virus Replication*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Tripartite Motif Proteins