{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:16:44Z","timestamp":1783037804887,"version":"3.54.6"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["6335\/5-1, 6335\/6-1, SFB1292\/2 TP02, CRC167\/2 project B16, CRC1470\/1 project A08, SFB1292\/2 TPQ0"],"award-info":[{"award-number":["6335\/5-1, 6335\/6-1, SFB1292\/2 TP02, CRC167\/2 project B16, CRC1470\/1 project A08, SFB1292\/2 TPQ0"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation for Experimental Biomedicine, Zurich, Switzerland","award":["6335\/5-1, 6335\/6-1, SFB1292\/2 TP02, CRC167\/2 project B16, CRC1470\/1 project A08, SFB1292\/2 TPQ01"],"award-info":[{"award-number":["6335\/5-1, 6335\/6-1, SFB1292\/2 TP02, CRC167\/2 project B16, CRC1470\/1 project A08, SFB1292\/2 TPQ01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enteroviruses (EV) are implicated in an extensive range of clinical manifestations, such as pancreatic failure, cardiovascular disease, hepatitis, and meningoencephalitis. We recently reported on the biochemical properties of the highly conserved cysteine residue at position 38 (C38) of enteroviral protein 3A and demonstrated a C38-mediated homodimerization of the Coxsackievirus B3 protein 3A (CVB3-3A) that resulted in its profound stabilization. Here, we show that residue C38 of protein 3A supports the replication of CVB3, a clinically relevant member of the enterovirus genus. The infection of HeLa cells with protein 3A cysteine 38 to alanine mutants (C38A) attenuates virus replication, resulting in comparably lower virus particle formation. Consistently, in a mouse infection model, the enhanced virus propagation of CVB3-3A wt in comparison to the CVB3-3A[C38A] mutant was confirmed and found to promote severe liver tissue damage. In contrast, infection with the CVB3-3A[C38A] mutant mitigated hepatic tissue injury and ameliorated the signs of systemic inflammatory responses, such as hypoglycemia and hypothermia. Based on these data and our previous report on the C38-mediated stabilization of the CVB3-3A protein, we conclude that the highly conserved amino acid C38 in protein 3A enhances the virulence of CVB3.<\/jats:p>","DOI":"10.3390\/v14040769","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T22:23:23Z","timestamp":1649370203000},"page":"769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Conserved Cysteine Residue in Coxsackievirus B3 Protein 3A with Implication for Elevated Virulence"],"prefix":"10.3390","volume":"14","author":[{"given":"Martin","family":"Voss","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Pinkert","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5897-8747","authenticated-orcid":false,"given":"Meike","family":"Kespohl","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung, Partner Side Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9456-3063","authenticated-orcid":false,"given":"Niclas","family":"Gimber","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Advanced Medical Bioimaging Core Facility, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-2498","authenticated-orcid":false,"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[{"name":"Cardiopathology, Institute for Pathology and Neuropathology, University of T\u00fcbingen, 72016 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Schmoranzer","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Advanced Medical Bioimaging Core Facility, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-9139","authenticated-orcid":false,"given":"Michael","family":"Laue","sequence":"additional","affiliation":[{"name":"Robert Koch Institute, Advanced Light and Electron Microscopy (ZBS 4), 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gaida","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany"},{"name":"Research Center for Immunotherapy, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany"},{"name":"Joint Unit Immunopathology, Institute of Pathology, University Medical Center, JGU-Mainz and TRON, Translational Oncology at the University Medical Center, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter-Michael","family":"Kloetzel","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, 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