ArticlePLoS pathogens2025
Circovirus Rep evades immune restriction by disrupting cGAS oligomerization and phase separation.
Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses.PLoS pathogens · 2026Article
- Development of Magnetic Particle-Based Chemiluminescence Immunoassays for Detecting PCV2 VLP- and Rep-Specific Antibodies and Their Combined Use for Immune Evaluation and Replication-Associated Exposure Assessment.Transboundary and emerging diseases · 2026Article
- Emerging Challenges and Advances in Porcine Circovirus: A Decade in Review.Transboundary and emerging diseases · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Cyclic GMP-AMP synthase (cGAS) is a key sensor of double-stranded DNA (dsDNA), initiating oligomerization and phase separation to drive immune responses against pathogens and endogenous damage. Porcine circovirus (PCV) induces immunosuppression, heightening susceptibility to secondary infections, but the underlying mechanisms remain unclear. Here, we report PCV type 2d (PCV2d) infection fails to induce type I interferons (IFN-I) and significantly suppresses IFN-I production upon poly (dA:dT) stimulation in a dose-dependent manner. Mechanistically, the replication-related protein (Rep) proteins of PCV2, PCV3 and PCV4 inhibit cGAS-mediated IFN-I induction by competitively binding dsDNA, thereby disrupting cGAS oligomerization and phase separation. Interestingly, Rep also suppresses mitochondria DNA-induced cGAS activation. We further identify Rep residues Q12 and R199-W202 as key regions facilitating dsDNA binding. Our findings reveal a previously unrecognized mechanism by which circovirus Rep antagonizes cGAS activation, providing new insights into PCV-induced immunosuppression.
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Registered trials
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