{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:28:50Z","timestamp":1793158130125,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32202818"],"award-info":[{"award-number":["32202818"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32202818"],"award-info":[{"award-number":["32202818"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the 2024 Annual Special Funds for Municipal-School Cooperation Projects of Yangzhou City","award":["YZ2024220"],"award-info":[{"award-number":["YZ2024220"]}]},{"award":["YZ2024220"],"award-info":[{"award-number":["YZ2024220"]}],"id":[{"id":"https:\/\/ror.org\/03mvs6080","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Open Project Program of Jiangsu Key Laboratory of Zoonosis","award":["R2304"],"award-info":[{"award-number":["R2304"]}]},{"name":"the Undergraduate Innovation and Entrepreneurship Training Program","award":["XCX20250789"],"award-info":[{"award-number":["XCX20250789"]}]},{"name":"the Undergraduate Innovation and Entrepreneurship Training Program","award":["XCX20250790"],"award-info":[{"award-number":["XCX20250790"]}]},{"name":"the Priority Academic Program Development of Jiangsu Higher Education Institutions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Manganese ions (Mn2+) are an essential trace element within organisms spanning the entire tree of life. It has reported that Mn2+ exerts strong immunocompetence effects and exhibits antiviral effects against various human and animal viruses, including DNA and RNA viruses. Recently, Mn2+ has been found to be involved in the activation of the innate immune DNA-sensing cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway and subsequent antiviral function. However, the antiviral mechanism of Mn2+ remains unclear. In the current study, the results suggest that the cGAS-STING pathway is essential for Mn2+ to promote interferon (IFN) signaling, but it is not essential for triggering antiviral functions. After knocking out the STING or interferon regulatory factor 3 (IRF3) gene, Mn2+ still retains its antiviral activity against herpes simplex virus type 1 (HSV-1) and vesicular stomatitis virus (VSV). Furthermore, the results from transcriptomic analysis indicate that Mn2+ can induce a significant change in the apoptotic process in STING\u2212\/\u2212 3D4\/21 cells. Mn2+ can induce cell apoptosis through the oxidative stress pathway, and inhibiting the apoptotic signal could suppress Mn2+-mediated antiviral activity in STING\u2212\/\u2212 3D4\/21 cells. Additionally, dual knockout of IRF3 and caspase3, resulting in concurrent loss of IFN and apoptotic signals, eliminates the antiviral effects of Mn2+. In summary, the current study suggests that Mn2+ could exert antiviral effects not only through the cGAS-STING-IFN pathway but also via the reactive oxygen species (ROS)-apoptosis pathway.<\/jats:p>","DOI":"10.3390\/vetsci13040396","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:30:36Z","timestamp":1776443436000},"page":"396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mn2+-Mediated Antiviral Activity Through Both the cGAS-STING-IFN and ROS-Apoptosis Pathways in Porcine Alveolar Macrophage Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0939-331X","authenticated-orcid":false,"given":"Wanglong","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou 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