Arrhythmias & electrophysiology
From Multi-Omics to Mechanism: Nucleocapsid–RCHY1–JUNB Axis Underlies SARS-CoV-2 Related Atrial Fibrillation Vulnerability
Authors' conclusion
Cardiac SARS-CoV-2 N protein promotes atrial inflammatory-fibrotic remodeling and AF vulnerability under chronic inflammatory conditions relevant to post-acute or prolonged COVID-19-related cardiovascular sequelae through RCHY1-dependent ubiquitination and stabilization of JUNB, identifying the N-RCHY1-JUNB axis as a mechanistically defined pathway for future therapeutic investigation.
Study context
- Population
- SARS-CoV-2-infected cardiac models and atrial fibrillation (AF) tissues (human transcriptomes); mice with cardiac SARS-CoV-2 N expression; modified cardiomyocytes
- Comparison
- Cardiac SARS-CoV-2 N expression and cardiac JUNB knockdown under repeated low-dose LPS
- Outcome
- Host pathways coupling viral factors to atrial remodeling and AF vulnerability
Methodological detailsmulti-cohort transcriptomic integration, mouse model, in vitro cardiomyocyte experiments
- Multi-cohort transcriptomic integration
- Mouse model
- In vitro cardiomyocyte experiments
Main finding
As reported in the abstract
JUNB hub identification and N-driven atrial remodeling and AF vulnerability
- JUNB identified as shared hub associated with SARS-CoV-2-related cardiac signaling and AF, with enrichment of inflammatory pathways relevant to atrial remodeling
- Cardiac N expression exacerbated atrial enlargement, inflammatory-fibrotic remodeling, AF inducibility and duration, and AERP shortening
- Cardiac JUNB knockdown attenuated these changes
- SARS-CoV-2 N enhanced JUNB-RCHY1 interaction, promoting K63-linked ubiquitination and stabilizing JUNB
- K36 identified as dominant ubiquitination site required for N-driven JUNB stabilization, TNF-α/NF-κB activation, and downstream inflammatory and fibrotic gene programs
- Chronic inflammatory model: repeated low-dose LPS
Original publication
From Multi-Omics to Mechanism: Nucleocapsid–RCHY1–JUNB Axis Underlies SARS-CoV-2 Related Atrial Fibrillation Vulnerability. Europace. Published 13 August 2026. doi:10.
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