TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Tripartite motif (TRIM) proteins are E3 ubiquitin ligases involved in cellular processes.
• TRIM proteins regulate host-virus interactions, but their role in rabies virus (RABV) infection is unclear.

Purpose of the Study:

• To investigate the role of TRIM proteins in RABV infection.
• To identify specific TRIM proteins that regulate RABV replication.
• To elucidate the mechanism by which TRIM44 affects RABV replication.

Main Methods:

• RNA sequencing (RNA-seq) to identify upregulated TRIM proteins in RABV-infected mouse neuroblastoma cells.
• Gene silencing (downregulation) and overexpression of TRIM44 to assess its effect on RABV replication.
• Pharmacological inhibition of autophagy using 3-MA and rapamycin to investigate the role of autophagy in TRIM44-mediated RABV replication.
• Analysis of LC3B expression and autophagosome formation.

Main Results:

• Several TRIM proteins were upregulated in RABV-infected cells.
• TRIM44 was identified as a key regulator, with its downregulation inhibiting and overexpression promoting RABV replication.
• TRIM44 promotes RABV replication via autophagy activation, as evidenced by the effects of autophagy inhibitors (3-MA and rapamycin) on RABV replication and autophagy markers (LC3B, autophagosome formation).

Conclusions:

• TRIM44 is a critical host factor that enhances RABV replication through an autophagy-dependent pathway.
• Modulating TRIM44 expression presents a potential therapeutic strategy for controlling rabies virus infection.