{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:01:01Z","timestamp":1791381661007,"version":"4.3.3"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004844","name":"National Cheng Kung University Hospital","doi-asserted-by":"publisher","award":["NCKUH\u201011404037"],"award-info":[{"award-number":["NCKUH\u201011404037"]}],"id":[{"id":"10.13039\/501100004844","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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The disease course of severe enterovirus (EV) infection with hepatic necrosis is usually fulminant and fatal. Coxsackievirus (CVB3) is the emerging and important serotype of newborn EV inducing hepatic necrosis. Calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) regulates host immunity, type I interferon (IFN\u2010I), and viral infections. The interaction of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , IFN\u2010I, and CVB3\u2010induced hepatitis remains to be investigated. To address these issues, we used the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    blocker manidipine, which reduces Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx into cells and is used in the clinic, the human hepatoma cell line (HuH7) for in vitro studies, and a murine infection model. In vitro results showed that CVB3 infection increased levels of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010binding proteins, calmodulin and calcineurin, which are IFN\u2010I suppressors. Moreover, manidipine decreased CVB3 titers in a manner dependent on IFN\u2010I. Mouse results revealed that manidipine reduced CVB3 lethality, viral loads, and organ damage of infected mice with elevated levels of IFN\u2010\u03b2 protein and mRNAs encoding IFN\u2010\u03b2 and interferon\u2010stimulated genes (ISGs), especially in the liver. Mechanism studies showed that manidipine enhanced the levels of mRNAs encoding IFN\u2010\u03b2 or ISG,\n                    <jats:italic>IFNB1<\/jats:italic>\n                    promoter activity, and IFN\u2010\u03b2 induction pathways of both RLR and STING in infected HuH7 cells. Overall, CVB3 infection increases Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx to suppress IFN\u2010\u03b2, and blocking Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx has the potential to reduce CVB3 infection by enhancing IFN\u2010\u03b2.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70938","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:23:46Z","timestamp":1777904626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Suppression of Calcium Influx Reduces Coxsackievirus B3 Lethality With Elevated Interferon Beta Responses in Mice"],"prefix":"10.1002","volume":"98","author":[{"given":"Yi\u2010Ling","family":"Hsiao","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences College of Medicine, National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Huei","family":"Hung","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences College of Medicine, National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Te","family":"Yeh","sequence":"additional","affiliation":[{"name":"Research, Institute for Microbial Diseases University of Osaka Osaka Japan"},{"name":"Center for Advanced Modalities and DDS (CAMaD) University of Osaka Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4585-9279","authenticated-orcid":false,"given":"Shun\u2010Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences College of Medicine, National Cheng Kung University Tainan Taiwan"},{"name":"Center of Infectious Disease and Signaling Research National Cheng Kung University Tainan Taiwan"},{"name":"Department of Microbiology and Immunology College of Medicine, National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"issue":"7","key":"e_1_2_9_2_1","first-page":"383","article-title":"Nonpolio Enterovirus Infection in the Neonate and Young Infant","volume":"10","author":"Hawkes M. 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