{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:00:01Z","timestamp":1788994801797,"version":"build-2803163510"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,2,23]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Previous studies dealing with the detection of enteroviral RNA in human endomyocardial biopsies have not differentiated between latent persistence of the enteroviral genome and active viral replication. Enteroviruses that are considered important factors for the development of myocarditis have a single-strand RNA genome of positive polarity that is transcribed by a virus-encoded RNA polymerase into a minus-strand mRNA during active viral replication. The synthesis of multiple copies of minus-strand enteroviral RNA therefore occurs only at sites of active viral replication but not in tissues with mere persistence of the viral genome.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014We investigated enteroviral RNA replication versus enteroviral RNA persistence in endomyocardial biopsies of 45 patients with left ventricular dysfunction and clinically suspected myocarditis. Using reverse-transcriptase polymerase chain reaction in conjunction with Southern blot hybridization, we established a highly sensitive assay to specifically detect plus-strand versus minus-strand enteroviral RNA in the biopsies. Plus-strand enteroviral RNA was detected in endomyocardial biopsies of 18 (40%) of 45 patients, whereas minus-strand RNA as an indication of active enteroviral RNA replication was detected in only 10 (56%) of these 18 plus-strand\u2013positive patients. Enteroviral RNA was not found in biopsies of the control group (n=26).\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014These data demonstrate that a significant fraction of patients with left ventricular dysfunction and clinically suspected myocarditis had active enteroviral RNA replication in their myocardium (22%). Differentiation between patients with active viral replication and latent viral persistence should be particularly important in future studies evaluating different therapeutic strategies. In addition, molecular genetic detection of enteroviral genome and differentiation between replicating versus persistent viruses is possible in a single endomyocardial biopsy.\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.7.889","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"889-895","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":152,"title":["Enteroviral RNA Replication in the Myocardium of Patients With Left Ventricular Dysfunction and Clinically Suspected Myocarditis"],"prefix":"10.1161","volume":"99","author":[{"given":"Matthias","family":"Pauschinger","sequence":"first","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Doerner","sequence":"additional","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Kuehl","sequence":"additional","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Schwimmbeck","sequence":"additional","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Poller","sequence":"additional","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Kandolf","sequence":"additional","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz-Peter","family":"Schultheiss","sequence":"additional","affiliation":[{"name":"From Medical Clinic II, University Hospital Benjamin Franklin, Freie Universita\u0308t Berlin (M.P., A.D., U.K., P.L.S., W.P., H.-P.S.); and the Department of Molecular Pathology, Institute for Pathology, Eberhard-Karls-Universita\u0308t (R.K.), Tu\u0308bingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","first-page":"1","volume":"11","year":"1989","unstructured":"Kandolf R, Hofschneider PH. Viral heart disease. Springer Semin Immunopathol. 1989;11:1\u201313.","journal-title":"Springer Semin Immunopathol"},{"key":"e_1_3_1_2_2","first-page":"425","volume":"101","year":"1980","unstructured":"Woodruff JF. Viral myocarditis: a review. Am J Pathol. 1980;101:425\u2013484.","journal-title":"Am J Pathol"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0890-8508(91)90033-G"},{"key":"e_1_3_1_4_2","first-page":"1120","volume":"17","year":"1986","unstructured":"Bowles NE, Richardson PJ, Olson EG, Archard LC. Detection of coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet. 1986;17:1120\u20131123.","journal-title":"Lancet"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.82.1.2163780"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)00517-T"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.6.8205668"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91509-1"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(83)80012-6"},{"key":"e_1_3_1_10_2","first-page":"3","volume":"1","year":"1987","unstructured":"Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JF, Olsen EG, Schoen FJ. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol. 1987;1:3\u201314.","journal-title":"Am J Cardiovasc Pathol"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.75.3.295"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1980.tb06030.x"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.239.4839.487"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.4.1573-1583.1990"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.14.4818"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.18.6133"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5273(88)90104-0"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.58.4.393"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508033330501"},{"key":"e_1_3_1_20_2","first-page":"112","volume":"17","year":"1992","unstructured":"Schultheiss H-P, K\u00fchl U, Janda I, Schannwell M, Strauer BE. Immunosuppressive therapie in myocarditis. Herz. 1992;17:112\u2013121.","journal-title":"Herz"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.56.6.628"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(89)90466-X"}],"updated-by":[{"DOI":"10.1161\/cir.0b013e3181e9c2dc","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T00:00:00Z","timestamp":1278979200000}}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.99.7.889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:51:25Z","timestamp":1715532685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.99.7.889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,2,23]]},"references-count":22,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1999,2,23]]}},"alternative-id":["10.1161\/01.CIR.99.7.889"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.99.7.889","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,2,23]]},"assertion":[{"value":"1998-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-11-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-02-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}