TRIM28 is a target for paramyxovirus V proteins

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• SUMO-modified TRIM28 (KAP1) represses endogenous retroelement (ERE) transcription, crucial for host antiviral immunity.
• Influenza A virus (IAV) infection can disrupt TRIM28 SUMOylation, activating immunity via ERE derepression.
• Other viruses may possess distinct mechanisms to evade this TRIM28-dependent defense.

Purpose of the Study:

• To investigate if paramyxoviruses engage with TRIM28 to counteract ERE-based antiviral immunity.
• To identify the molecular basis for TRIM28 engagement by paramyxovirus V proteins.
• To determine the functional consequences of paramyxovirus V protein interaction with TRIM28.

Main Methods:

• Co-immunoprecipitation assays to assess TRIM28-V protein interactions.
• Site-directed mutagenesis to map critical residues in V proteins and TRIM28 domains.
• Quantitative PCR to measure HERVK14C RNA induction.
• Viral infection experiments to evaluate TRIM28 SUMOylation status and immune response.

Main Results:

• V proteins from diverse paramyxoviruses (Measles, Mumps, Parainfluenza, Nipah/Hendra) bind to TRIM28, with varying efficiencies.
• Specific C-terminal residues of V proteins and TRIM28 domains (Coiled-Coil, PHD-Bromodomain) mediate this interaction.
• Paramyxovirus infection prevents loss of SUMO-modified TRIM28 and HERVK14C induction, unlike IAV.
• Pre-infection with Parainfluenza virus type 2 limits IAV-induced TRIM28 modification loss and HERVK14C upregulation.

Conclusions:

• Paramyxoviruses employ V proteins to antagonize the TRIM28-regulated ERE-based antiviral defense system.
• This interaction preserves TRIM28 SUMOylation, inhibiting ERE derepression and immunostimulatory RNA production.
• These findings highlight a novel viral immune evasion strategy and support the role of TRIM28 in innate immunity.