{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:39:47Z","timestamp":1786621187427,"version":"build-2736575974"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background and Aims<\/jats:title>\n SARS-CoV-2 exposure has been linked to cardiovascular complications, including atrial fibrillation (AF), but the host pathways coupling viral factors to atrial remodeling and AF vulnerability remain incompletely understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We integrated multi-cohort human transcriptomes from SARS-CoV-2\u2013infected cardiac models and AF tissues, applied WGCNA and machine-learning\u2013based feature selection, and profiled immune infiltration. To approximate a sustained low-grade inflammatory milieu relevant to prolonged COVID-19-related cardiovascular sequelae, mice with cardiac SARS-CoV-2 N expression underwent repeated low-dose LPS administration. JUNB loss-of-function was evaluated by rAAV9-mediated cardiac knockdown, with echocardiographic, electrophysiological, histological, and molecular phenotyping. Mechanistic studies were performed in modified cardiomyocytes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Integrated transcriptomic analyses identified JUNB as a shared hub associated with SARS-CoV-2-related cardiac signaling and AF, with enrichment of inflammatory pathways relevant to atrial remodeling. In the chronic inflammatory model, cardiac N expression exacerbated atrial enlargement, inflammatory-fibrotic remodeling, AF inducibility and duration, and AERP shortening, whereas cardiac JUNB knockdown attenuated these changes. Mechanistically, co-immunoprecipitation and in-cell ubiquitination assays showed that SARS-CoV-2 N enhanced the JUNB-RCHY1 interaction, promoting K63-linked ubiquitination and stabilizing JUNB. Site-mapping and functional assays identified K36 as the dominant ubiquitination site required for N-driven JUNB stabilization, TNF-\u03b1\/NF-\u03baB activation, and downstream inflammatory and fibrotic gene programs.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/europace\/euag207","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:44:54Z","timestamp":1785930294000},"source":"Crossref","is-referenced-by-count":0,"title":["From Multi-Omics to Mechanism: Nucleocapsid\u2013RCHY1\u2013JUNB Axis Underlies SARS-CoV-2 Related Atrial Fibrillation Vulnerability"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4111-8659","authenticated-orcid":false,"given":"Chengyu","family":"Xiang","sequence":"first","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-1578","authenticated-orcid":false,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Children's Hospital of Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5983-1960","authenticated-orcid":false,"given":"Yan","family":"Hua","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9586-898X","authenticated-orcid":false,"given":"Ruijie","family":"Xu","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youfu","family":"Huang","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7068-9689","authenticated-orcid":false,"given":"Albrecht","family":"Von Brunn","sequence":"additional","affiliation":[{"name":"Max-von-Pettenkofer Institute, Virology department, Ludwig-Maximilians-University Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0125-3926","authenticated-orcid":false,"given":"Fengxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital with Nanjing Medical University , Nanjing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,13]]},"container-title":["Europace"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/europace\/advance-article-pdf\/doi\/10.1093\/europace\/euag207\/70632564\/euag207.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/europace\/advance-article-pdf\/doi\/10.1093\/europace\/euag207\/70632564\/euag207.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:21:33Z","timestamp":1786620093000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/europace\/advance-article\/doi\/10.1093\/europace\/euag207\/8760858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/europace\/euag207","relation":{},"ISSN":["1099-5129","1532-2092"],"issn-type":[{"value":"1099-5129","type":"print"},{"value":"1532-2092","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"article-number":"euag207"}}