{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:25:19Z","timestamp":1786958719908,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"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":["32573466"],"award-info":[{"award-number":["32573466"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32573466"],"award-info":[{"award-number":["32573466"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong Academy of Agricultural Sciences Young Scientific Talent Recruitment Program","award":["R2024YJ-QG001"],"award-info":[{"award-number":["R2024YJ-QG001"]}]},{"name":"Sub project of \u201cDiscipline Construction of Swine and Poultry Breeding Industry\u201d of Special Project on Science and Technology Innovation Strategy","award":["ZX202501-02"],"award-info":[{"award-number":["ZX202501-02"]}]},{"name":"Young Scientific Talent Development Program, Institute of Animal Health, Guangdong Academy of Agricultural Sciences","award":["PY2024004"],"award-info":[{"award-number":["PY2024004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Superoxide dismutase 2 (SOD2), a key mitochondrial antioxidant enzyme, is essential for maintaining cellular redox homeostasis by scavenging superoxide radicals. While viruses often induce oxidative stress, the specific role of SOD2 in antiviral defense remains unclear. Here, we report that vaccinia virus (VACV) infection triggers mitochondrial and cellular reactive oxygen species (ROS) and selectively upregulates SOD2, but not SOD1. Genetic knockout of SOD2 exacerbated mitochondrial ROS (mtROS) accumulation and significantly enhanced VACV replication and spread, resulting in larger viral plaques. Conversely, SOD2 overexpression constrained plaque formation and suppressed viral dissemination. Mechanistically, the antiviral function of SOD2 does not strictly rely on its enzymatic activity or mitochondrial targeting, as neither the deacetylation-mimicking mutant nor the mutant lacking the mitochondrial localization signal peptide appreciably impaired its antiviral potency. Furthermore, in a rabbit model, local overexpression of human SOD2 attenuated the poxvirus lesion formation. Our findings unveil an important yet easily overlooked role of SOD2 in antiviral defense and posit it as a promising candidate for the development of host-directed therapeutics against poxviruses.<\/jats:p>","DOI":"10.3390\/antiox15081019","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:05:41Z","timestamp":1786953941000},"page":"1019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Important Role of Superoxide Dismutase 2 in Controlling Poxvirus Proliferation and Pathogenicity"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaoshuang","family":"Shi","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Key Laboratory of Livestock Disease Prevention of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonoses Prevention and Control, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Key Laboratory of Livestock Disease Prevention of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonoses Prevention and Control, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonoses Prevention and Control, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3411-3196","authenticated-orcid":false,"given":"Quan","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory, Hengqin 519031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Key Laboratory of Livestock Disease Prevention of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3267-1859","authenticated-orcid":false,"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonoses Prevention and Control, Academy of Military Medical Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-4858","authenticated-orcid":false,"given":"Shouwen","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, Key Laboratory of Livestock Disease Prevention of Guangdong Province, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.tim.2021.12.011","article-title":"Mitochondria-Mediated Oxidative Stress During Viral Infection","volume":"30","author":"Foo","year":"2022","journal-title":"Trends Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000452160","article-title":"Nonstructural Protein 1 of Tick-Borne Encephalitis Virus Induces Oxidative Stress and Activates Antioxidant Defense by the Nrf2\/Are Pathway","volume":"59","author":"Kuzmenko","year":"2016","journal-title":"Intervirology"},{"key":"ref_3","first-page":"520","article-title":"The Bridge between Cell Survival and Cell Death: Reactive Oxygen Species-Mediated Cellular Stress","volume":"22","year":"2023","journal-title":"EXCLI 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