{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:14:49Z","timestamp":1784052889954,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014392","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32503033"],"award-info":[{"award-number":["32503033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014103","name":"Key Technology Research and Development Program of Shandong Province","doi-asserted-by":"publisher","award":["2022CXPT005"],"award-info":[{"award-number":["2022CXPT005"]}],"id":[{"id":"10.13039\/100014103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015335","name":"Modern Agricultural Technology Industry System of Shandong province","doi-asserted-by":"publisher","award":["SDAIT-11-03"],"award-info":[{"award-number":["SDAIT-11-03"]}],"id":[{"id":"10.13039\/501100015335","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Mitochondrial metabolic homeostasis serves as a critical checkpoint that integrates cellular bioenergetics with innate immunity. While viruses often subvert mitochondrial functions to manipulate cell fate, the specific viral determinants that directly reprogram host metabolic enzymes to drive inflammatory injury remain incompletely defined. Here, using infection with a highly virulent novel duck reovirus (NDRV) strain as a model of systemic immunopathology, we identify the viral capsid protein \u03c3C as a metabolic virulence factor. We show that \u03c3C binds to the mitochondrial targeting sequence (MTS) of COQ6, a conserved monooxygenase required for coenzyme Q10 (CoQ10) biosynthesis, and blocks its mitochondrial import, thereby disrupting CoQ10 homeostasis. This metabolic blockade induces mitochondrial dysfunction, characterized by mtROS accumulation and the cytosolic release of oxidized mitochondrial DNA (ox-mtDNA). We demonstrate that ox-mtDNA acts as a danger signal that triggers NLRP3 activation and downstream gasdermin E (GSDME)-dependent pyroptosis. Moreover, \u03c3C knockdown in infected cells reduces ox-mtDNA release and attenuates pyroptosis. CoQ10 supplementation restores mitochondrial homeostasis and alleviates NDRV-induced inflammatory pathology\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    without detectably reducing viral RNA loads, consistent with a host-directed disease tolerance mechanism. Collectively, these findings define a \u03c3C\u2013COQ6\u2013CoQ10\u2013ox-mtDNA\u2013NLRP3 axis that links a structural avian orthoreovirus protein to metabolic reprogramming and highlight the COQ6\u2013CoQ10 pathway as a tractable therapeutic target for limiting virus-induced inflammatory tissue damage.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014392","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:38:46Z","timestamp":1783445926000},"page":"e1014392","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel duck reovirus \u03c3C hijacks the mitochondrial COQ6\u2013CoQ10 axis to drive NLRP3-dependent pyroptosis"],"prefix":"10.1371","volume":"22","author":[{"given":"Hui","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Bei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengxiang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7778-1509","authenticated-orcid":true,"given":"Ruihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"issue":"1","key":"ppat.1014392.ref001","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.02096-21","article-title":"Mitochondria 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