{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:07:38Z","timestamp":1791648458983,"version":"4.3.4"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["32170125"],"award-info":[{"award-number":["32170125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Research and development program in key areas of Guangdong Province","award":["2021B0707010009"],"award-info":[{"award-number":["2021B0707010009"]}]},{"name":"the Zhaoqing Science and Technology Projects","award":["2021C001"],"award-info":[{"award-number":["2021C001"]}]},{"name":"the Zhaoqing Xijiang Innovative Team Foundation of China","award":["P2021154-0202"],"award-info":[{"award-number":["P2021154-0202"]}]},{"name":"the independent project of Zhaoqing Branch Center of Guangdong Laboratory of Lingnan Modern Agricultural Science and Technology","award":["P20211154-0105"],"award-info":[{"award-number":["P20211154-0105"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Porcine epidemic diarrhea virus (PEDV) is a primary cause of viral diarrhea in neonatal piglets, leading to substantial economic losses in the swine industry globally. It primarily targets epithelial cells of the small intestine, compromising intestinal function and resulting in the death of affected animals. As mitochondria are essential for maintaining gut health, this study investigates the effects of PEDV infection on mitochondrial function in small intestinal epithelial cells and its subsequent impacts. Using small RNA sequencing, fluorescence\n              <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n              hybridization, dual luciferase reporter assay, gene overexpression, and silencing experiments, we investigated the mitochondrial structural and functional impairments induced by PEDV infection in jejunum epithelial cells of piglets and characterized the regulatory pattern of miRNAs in mitochondria of jejunum epithelial cells during PEDV infection. The results indicate that PEDV infection leads to the upregulation and mitochondrial localization of the nuclear-encoded microRNA, miR-34c, which in turn suppresses COX1 expression. The activation of the miR-34c\/COX1 axis diminishes mitochondrial complex III, IV, and V activities, depletes ATP, lowers mitochondrial oxygen consumption, induces mitochondrial depolarization, increases the accumulation of mitochondrial reactive oxygen species (mtROS), and stimulates mitophagy. Furthermore, we confirm that CREB3L1 acts as an upstream transcription factor regulating the miR-34c\/COX1 axis during PEDV infection, modulating mitochondrial damage in the epithelial cells of the jejunum. These findings demonstrate for the first time that PEDV infection activates the miR-34c\/COX1 axis via the transcription factor CREB3L1 and regulates the nuclear-mitochondrial communication and mitochondrial fate, providing a new perspective on the pathogenesis of PEDV.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>This study reveals the mechanism by which the porcine epidemic diarrhea virus (PEDV) disrupts mitochondrial function in piglets, enhancing viral pathogenicity. By demonstrating how PEDV infection upregulates miR-34c, leading to COX1 suppression and subsequent mitochondrial dysfunction, the research highlights a novel aspect of viral manipulation of host cellular mechanisms. These findings provide a deeper understanding of the PEDV pathogenesis and identify potential targets for therapeutic intervention, advancing efforts to mitigate the economic impact of PEDV on the swine industry.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00591-24","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T13:00:46Z","timestamp":1741784446000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Induction of mitochondrial damage via the CREB3L1\/miR-34c\/COX1 axis by porcine epidemic diarrhea virus infection facilitates pathogenicity"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3053-8009","authenticated-orcid":false,"given":"Hangao","family":"Xie","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xiong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlian","family":"Guan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Han","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixuan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-2948","authenticated-orcid":false,"given":"Dingxiang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]},{"name":"Integrative Microbiology Research Centre, South China Agricultural University Integrative Microbiology Research Centre","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiai","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Zhaoqing Branch Centre of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology","place":["Zhaoqing, China"]},{"name":"Key Laboratory of Manufacture Technology of Veterinary Bioproducts, Ministry of Agriculture and Rural Affairs","place":["Beijing, China"]},{"name":"Guangdong Enterprise Key Laboratory of Biotechnology R&D of Veterinary Biologics","place":["Zhaoqing, China"]},{"name":"Zhaoqing Dahuanong Biology Medicine Co. 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