{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:20:00Z","timestamp":1784647200960,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["IV\u2010113\u2010PP\u201011"],"award-info":[{"award-number":["IV\u2010113\u2010PP\u201011"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), the causative agent of COVID\u201019, has resulted in more than 7.1 million deaths worldwide since 2019 and is increasingly recognized for its cardiovascular complications beyond respiratory disease. Growing evidence suggests that the SARS\u2010CoV\u20102 spike protein itself, present during infection or after vaccination, may directly contribute to cardiac dysfunction, including myocarditis, through interaction with angiotensin\u2010converting enzyme 2 (ACE2) receptors expressed in cardiomyocytes. To investigate these effects, we established a lentiviral\u2010based SARS\u2010CoV\u20102 pseudovirus system expressing spike proteins from the Wuhan and Delta variants and examined their impact on human embryonic stem cell\u2013derived cardiomyocytes (ESC\u2010CMs). Exposure to pseudovirus resulted in significant increases in sarcomere length and promoted syncytium formation in ESC\u2010CMs. Moreover, infection with either Wuhan or Delta spike pseudoviruses caused marked early disturbances in intracellular calcium transient dynamics as early as 1.5 hours post\u2010infection, with partial recovery observed by 24 hours. Transcriptomic analyses further revealed significant dysregulation of key cardiac\u2010related genes involved in cell junction organization, structural integrity, ion channel function, and calcium handling. Together, these findings demonstrate the utility of a lentiviral pseudovirus platform for modeling SARS\u2010CoV\u20102\u2013induced cardiac injury and highlight a direct pathogenic role of the spike protein in cardiac structural, functional, and molecular abnormalities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jmv.70789","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:32:04Z","timestamp":1767713524000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SARS\u2010CoV\u20102 Spike Protein\u2010Mediated Cardiac Dysfunction: Structural Abnormalities, Impaired Calcium Dynamics, and Gene Expression Changes in Human Stem Cell\u2010Derived Cardiomyocytes"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9932-5651","authenticated-orcid":false,"given":"Chen\u2010Yu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Health Sciences Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Center for Stem Cell Research, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Physics and Astronomy Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3513-1879","authenticated-orcid":false,"given":"Chia\u2010Chi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayna","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3243-9102","authenticated-orcid":false,"given":"Sheng\u2010Hsuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-0948","authenticated-orcid":false,"given":"Chiao\u2010Hsuan","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"},{"name":"Department of Medical Laboratory and Regenerative Medicine MacKay Medical University New Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Yen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-4046","authenticated-orcid":false,"given":"Jen\u2010Ren","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology National Cheng Kung University Tainan Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Health Sciences Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes Tainan Taiwan"},{"name":"Center of Infectious Diseases and Signaling Research National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bsheal.2020.11.002"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc0870"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0400-4"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2113874119"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10010001"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2895-3"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.043"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12982"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108891"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010951"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01769-3"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011901"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00751-24"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","unstructured":"C.Guo Y.Yu J.Liu et al. \u201cAntigenic and Virological Characteristics of SARS\u2010CoV\u20102 Variant BA.3.2 XFG and NB.1.8.1. \u201d bioRxiv 0 (2025):2025.04.30.651462.","DOI":"10.1101\/2025.04.30.651462"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0968-3"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13971"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.100855"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.24110"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.061025"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.3551"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-025-01139-4"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.150"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319060"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.07.012"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00134-25"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100052"},{"key":"e_1_2_13_28_1","unstructured":"N.Vischer \u201cPeakFinder Tool \u201d published 2013 https:\/\/sils.fnwi.uva.nl\/bcb\/objectj\/examples\/PeakFinder\/peakfinder.html."},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13122485"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03944-y"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04266-9"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00023.2006"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.08.020"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a059928"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.256495"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.986107"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0490"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202213200"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.12.017"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2022.05.055"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202101327"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-024-01280-y"},{"issue":"4","key":"e_1_2_13_43_1","first-page":"187","article-title":"Comparative Severity of COVID\u201019 Cases Caused by Alpha, Delta or Omicron SARS\u2010CoV\u20102 Variants and Its Association With Vaccination","volume":"42","author":"Varea\u2010Jim\u00e9nez E.","year":"2023","journal-title":"Enfermedades Infecciosas y Microbiolog\u00eda Cl\u00ednica (English Ed)"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-105963\/v1"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.8.2306"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03491-6"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106267"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/9000598"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31401-5"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.059970"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00369-4"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70789","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.70789","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T05:40:04Z","timestamp":1769492404000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.70789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jmv.70789"],"URL":"https:\/\/doi.org\/10.1002\/jmv.70789","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70789"}}