Pseudorabies virus tegument protein UL13 recruits RNF5 to inhibit STING-mediated antiviral immunity

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Pseudorabies virus (PRV) employs immune evasion strategies to counteract host defenses.
• The cGAS-STING signaling pathway is crucial for detecting viral infections and initiating antiviral responses.
• The precise mechanisms by which PRV proteins interfere with the cGAS-STING axis remain largely unknown.

Purpose of the Study:

• To investigate whether PRV-encoded proteins modulate the cGAS-STING pathway for immune evasion.
• To elucidate the specific role of PRV tegument protein UL13 in regulating STING-mediated antiviral signaling.

Main Methods:

• Co-immunoprecipitation assays to identify protein interactions.
• Ubiquitination assays to determine ubiquitination patterns.
• Western blotting to assess protein stability and degradation.
• Viral infection models in cell culture and mice to evaluate pathogenicity and immune responses.

Main Results:

• PRV tegument protein UL13 directly interacts with STING.
• UL13 recruits the E3 ligase RNF5 to promote STING ubiquitination and degradation.
• UL13 deficiency in PRV leads to enhanced type I interferon production and reduced pathogenicity in mice.
• RNF5 deficiency enhances antiviral responses against PRV infection.

Conclusions:

• PRV UL13 inhibits STING-mediated antiviral signaling by promoting STING degradation.
• This represents a novel mechanism of viral immune evasion targeting the cGAS-STING pathway.
• UL13 antagonism of STING contributes to PRV's ability to evade host antiviral immunity and establish persistent infections.