{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:18:29Z","timestamp":1785449909653,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO.82002147 and NO.82073618"],"award-info":[{"award-number":["NO.82002147 and NO.82073618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["NO.2019M662543"],"award-info":[{"award-number":["NO.2019M662543"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Scientific Research Project of Henan Institution of Higher Education","award":["NO.20A330004 and NO.21A310026"],"award-info":[{"award-number":["NO.20A330004 and NO.21A310026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may be one of the causes of death. However, the mechanisms of CVA2-induced heart injury have not been well understood. In this study, we used a neonatal mouse model of CVA2 to investigate the possible mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart tissues from infected mice. The activity of total aspartate transaminase (AST) and lactate dehydrogenase (LDH) was notably increased in heart tissues from infected mice. CVA2 infection also led to the disruption of cell-matrix interactions in heart tissues, including the increases of matrix metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45+ and CD11b+ cells) were observed in heart tissues of infected mice. Correspondingly, the expression levels of inflammatory cytokines in tissue lysates of hearts, including tumor necrosis factor alpha (TNF-\u03b1), interleukin-1beta (IL-1\u03b2), IL6 and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in CVA2 infected mice. Inflammatory signal pathways in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-\u03baB), were also activated after infection. In summary, CVA2 infection leads to heart injury in a neonatal mouse model, which might be related to viral replication, increased expression levels of MMP-related enzymes and excessive inflammatory responses.<\/jats:p>","DOI":"10.3390\/v13081588","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T08:35:52Z","timestamp":1628670952000},"page":"1588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Wangquan","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2447-0827","authenticated-orcid":false,"given":"Peiyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7854-4652","authenticated-orcid":false,"given":"Ling","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-0310","authenticated-orcid":false,"given":"Shuaiyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-0808","authenticated-orcid":false,"given":"Yuefei","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangcai","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China"},{"name":"Henan Key Laboratory of Molecular Medicine, Zhengzhou University, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1007\/s00705-020-04734-z","article-title":"Molecular Epidemiology of Enteroviruses Associated with Severe Hand, Foot and Mouth Disease in Shenzhen, China, 2014\u20132018","volume":"165","author":"Chen","year":"2020","journal-title":"Arch. 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