{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:01:09Z","timestamp":1772164869268,"version":"3.50.1"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">We infected C57Bl\/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose\u2010response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling noncompaction (23.5%), and double\u2010outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers and severity of congenital heart defects, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of congenital heart defects. We examined signaling pathways in CVB3\u2010exposed hearts using RNA sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor\u2010\u03b21, and extracellular matrix proteins were the most highly enriched in CVB3\u2010infected fetuses with ventricular septal defects. Moreover, cardiomyocyte proliferation was 50% lower in fetuses with ventricular septal defects compared with uninfected controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">We conclude prenatal CVB3 infection induces congenital heart defects. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for most of observed phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.120.017995","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T05:14:56Z","timestamp":1610601296000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Coxsackievirus B3 Infection Early in Pregnancy Induces Congenital Heart Defects Through Suppression of Fetal Cardiomyocyte Proliferation"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-4963","authenticated-orcid":false,"given":"Vipul","family":"Sharma","sequence":"first","affiliation":[{"name":"Division of Pediatric Cardiothoracic Surgery Department of Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa S.","family":"Goessling","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiothoracic Surgery Department of Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anoop K.","family":"Brar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiothoracic Surgery Department of Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3637-8414","authenticated-orcid":false,"given":"Chetanchandra S.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Washington University School of Medicine St. Louis MO"},{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-8677","authenticated-orcid":false,"given":"Indira U.","family":"Mysorekar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Washington University School of Medicine St. Louis MO"},{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-8391","authenticated-orcid":false,"given":"Pirooz","family":"Eghtesady","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiothoracic Surgery Department of Surgery Washington University School of Medicine St. Louis MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.023544"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.03.491"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.023544"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(200024)97:4<304::AID-AJMG1281>3.0.CO;2-#"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2016.1169526"},{"key":"e_1_3_2_7_2","first-page":"279","article-title":"Some comments on the 1964\u201365 epidemic in California","volume":"109","author":"Kleinman DS","year":"1968","unstructured":"Kleinman DS, Poole BD, Beckman GM, Hammersly MF, Rubella MTA. 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