TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Rabies virus (RABV) poses a significant global public health risk, with incompletely understood infection mechanisms and limited treatment options.
• Host restriction factors are crucial for controlling viral replication and developing antiviral therapies.
• Tripartite motif-containing (TRIM) proteins are known regulators of viral replication and innate immune responses.

Purpose of the Study:

• To investigate the role of TRIM25 in RABV infection.
• To elucidate the mechanism by which TRIM25 affects RABV replication.
• To identify TRIM25 as a potential therapeutic target for rabies.

Main Methods:

• Next-generation sequencing to assess TRIM25 expression during infection.
• Gene knockdown and overexpression techniques to study TRIM25 function.
• Interferon and RIG-I knockdown experiments to analyze the signaling pathway involved.
• Analysis of TRIM25 interaction with viral proteins.

Main Results:

• TRIM25 expression is upregulated during HEP-Flury infection.
• TRIM25 knockdown enhances viral production, while overexpression suppresses it.
• TRIM25 regulates the type-I interferon response by targeting RIG-I, indicating a RIG-I-IFN axis involvement.
• TRIM25 does not directly interact with HEP-Flury structural proteins.

Conclusions:

• TRIM25 functions as a host restriction factor against RABV infection.
• TRIM25 inhibits RABV replication through the RIG-I-interferon signaling pathway.
• TRIM25 represents a potential novel target for antiviral drug development against rabies.