TRIM29 inhibits PRRSV replication by targeting nsp11 for degradation

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Ubiquitination is crucial in viral infections.
• Porcine reproductive and respiratory syndrome virus (PRRSV) nsp11 is an endoribonuclease vital for viral replication.
• PRRSV nsp11 suppresses host interferon production.

Purpose of the Study:

• To investigate the ubiquitination of PRRSV nsp11.
• To identify host factors regulating nsp11 stability and function.
• To elucidate the mechanism by which PRRSV evades host immunity.

Main Methods:

• Site-directed mutagenesis to create ubiquitination-deficient nsp11 mutants.
• Western blot analysis to detect ubiquitination and protein levels.
• Co-immunoprecipitation to identify interacting host proteins.
• Interferon reporter assays to assess antiviral activity.
• Viral replication assays.

Main Results:

• PRRSV nsp11 undergoes K48-linked polyubiquitination at lysine 173 (K173).
• Ubiquitination targets nsp11 for degradation by the ubiquitin-proteasome system (UPS).
• The host E3 ubiquitin ligase TRIM29 binds nsp11 and mediates its K48-linked ubiquitination and degradation.
• TRIM29-mediated degradation of nsp11 inhibits viral replication by restoring interferon production.
• This ubiquitination mechanism is conserved in most arteriviruses.

Conclusions:

• PRRSV nsp11 is regulated by UPS-mediated degradation via K48-linked ubiquitination at K173.
• TRIM29 acts as a host restriction factor by degrading nsp11, thereby inhibiting PRRSV.
• This conserved mechanism highlights a critical host-pathogen interaction in arteriviral infections.