{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:24:05Z","timestamp":1785461045748,"version":"3.56.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Coxsackie-B-viruses (CVB) are frequent causes of acute myocarditis and dilated cardiomyopathy, but an effective antiviral therapy is still not available. Previously, we and others have demonstrated that treatment with an engineered sCAR-Fc (soluble coxsackievirus-adenovirus receptor fused to the carboxyl-terminus of human IgG) efficiently neutralizes CVB3 and inhibits the development of cardiac dysfunction in mice with acute CVB3-induced myocarditis. In this study, we analyzed the potential of sCAR-Fc for treatment of chronic CVB3-induced myocarditis in an outbred NMRI mouse model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>NMRI mice were infected with the CVB3 strain 31-1-93 and treated with a sCAR-Fc expressing adeno-associated virus 9 vector 1, 3, and 7 days after CVB3 infection. Chronic myocarditis was analyzed on day 28 after infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Initial investigations showed that NMRI mice develop pronounced chronic myocarditis between day 18 and day 28 after infection with the CVB3 strain 31-1-93. Chronic cardiac infection was characterized by inflammation and fibrosis as well as persistence of viral genomes in the heart tissue and by cardiac dysfunction. Treatment of NMRI mice resulted in a distinct reduction of cardiac inflammation and fibrosis and almost complete elimination of virus RNA from the heart by day 28 after infection. Moreover, hemodynamic measurement revealed improved cardiac contractility and diastolic relaxation in treated mice compared with mice treated with a control vector (mean\u00b1SD; maximal pressure, 81.9\u00b19.2 versus 69.4\u00b18.6 mm\u2009Hg,\n              <jats:italic>P<\/jats:italic>\n              =0.02; left ventricular ejection fraction, 68.9\u00b18.5 versus 54.2\u00b111.5%,\n              <jats:italic>P<\/jats:italic>\n              =0.02; dP\/dt\n              <jats:sub>max<\/jats:sub>\n              , 7275.2\u00b11674 versus 4432.6\u00b11107 mm\u2009Hg\/s,\n              <jats:italic>P<\/jats:italic>\n              =0.004; dP\/dt\n              <jats:sub>min<\/jats:sub>\n              , \u22124046.9\u00b1776 versus \u22123146.3\u00b1642 mm\u2009Hg\/s,\n              <jats:italic>P<\/jats:italic>\n              =0.046). The therapeutic potential of sCAR-Fc is limited, however, since postponed start of sCAR-Fc treatment either 3 or 7 days after infection could not attenuate myocardial injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Early therapeutic employment of sCAR-Fc, initiated at the beginning of the primary viremia, inhibits the development of chronic CVB3-induced myocarditis and improves the cardiac function to a level equivalent to that of uninfected animals.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.119.005250","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T10:00:16Z","timestamp":1573639216000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Early Treatment of Coxsackievirus B3\u2013Infected Animals With Soluble Coxsackievirus-Adenovirus Receptor Inhibits Development of Chronic Coxsackievirus B3 Cardiomyopathy"],"prefix":"10.1161","volume":"12","author":[{"given":"Sandra","family":"Pinkert","sequence":"first","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Institute of Biochemistry, Germany (S.P., A.B.)."},{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, Germany (S.P., B.D., M.P., J.K., H.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babette","family":"Dieringer","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, Germany (S.P., B.D., M.P., J.K., H.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Klopfleisch","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Freie Universit\u00e4t Berlin, Germany (R.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Savvatis","sequence":"additional","affiliation":[{"name":"Inherited Cardiovascular Diseases Unit, Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom (K.S.)."},{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Van Linthout","sequence":"additional","affiliation":[{"name":"Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Klinikum, Germany (S.V.L., C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markian","family":"Pryshliak","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, Germany (S.P., B.D., M.P., J.K., H.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Tsch\u00f6pe","sequence":"additional","affiliation":[{"name":"Berlin-Brandenburg Center for Regenerative Therapies, Campus Virchow Klinikum, Germany (S.V.L., C.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[{"name":"Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Germany (K.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kurreck","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, Germany (S.P., B.D., M.P., J.K., H.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Beling","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Fechner","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, Germany (S.P., B.D., M.P., J.K., H.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn296"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-003-0213-y"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000155616.07901.35"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.99.7.889"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.89.6.2582"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.548156"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.12.019"},{"key":"e_1_3_5_9_2","first-page":"369","article-title":"Coxsackievirus B3-induced chronic myocarditis in outbred NMRI mice","volume":"2","author":"Merkle I","year":"1999","unstructured":"Merkle, I, Tonew, M, Gl\u00fcck, B, Schmidtke, M, Egerer, R, Stelzner, A. Coxsackievirus B3-induced chronic myocarditis in outbred NMRI mice. J Hum Virol. 1999;2:369\u2013379.","journal-title":"J Hum Virol"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20933"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1993.1113"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-9071(199706)52:2<206::aid-jmv15>3.0.co;2-i"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/16.suppl_o.56"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5304.1320"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.5"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.99.8.1091"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000049349.56211.09"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/382598"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.05.016"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.845339"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.18.12016-12024.2005"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.1.655-660.2005"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2002.01924.x"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.10.010"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu504"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0934-8840(11)80801-7"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2015.19"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.03.014"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306573"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.09.074"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.11.8098-8108.1996"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0003-4975(96)00946-0"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0363-x"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.276"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1416"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2014.11.030"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-003-0199-5"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2005.7"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.74.2.182"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.119.005250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:39:25Z","timestamp":1715564365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.119.005250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.119.005250"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.119.005250","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11]]},"assertion":[{"value":"2019-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e005250"}}