TRIM7 Inhibits Rabies Virus Replication by Promoting K48-Linked Ubiquitination and Degradation of RABV-M

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Rabies virus (RABV) poses a significant global health threat due to its high mortality rate and lack of specific treatments.
• Triple-motif protein 7 (TRIM7) is involved in innate immunity against viral infections, but its role in rabies is unknown.

Purpose of the Study:

• To investigate the function of TRIM7 in the context of RABV infection.
• To identify potential therapeutic targets for rabies treatment.

Main Methods:

• RNA sequencing (RNA-seq) to identify differentially expressed TRIM proteins in RABV-infected cells.
• Gene knockdown and overexpression experiments to assess TRIM7's effect on RABV replication.
• Co-immunoprecipitation and ubiquitination assays to determine the interaction and mechanism between TRIM7 and RABV matrix protein (M).

Main Results:

• TRIM7 expression was upregulated in RABV-infected cells.
• TRIM7 knockdown enhanced RABV replication, while TRIM7 overexpression inhibited it.
• TRIM7 directly interacted with RABV-M, promoting its K48-linked ubiquitination and proteasomal degradation.
• Lysine 115 (K115) on RABV-M was identified as a key site for TRIM7-mediated degradation.

Conclusions:

• TRIM7 acts as a host antiviral factor that restricts RABV replication.
• TRIM7 inhibits RABV by inducing the ubiquitination and degradation of the viral M protein.
• TRIM7 represents a promising novel therapeutic target for rabies treatment.