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Given that lipid peroxides in the liver are key mediators of cell proliferation and death, the role and regulation of endogenous lipid peroxide metabolism in response to coronavirus infection need to be illuminated. The enzymatic activities of SOD, CAT, mitochondrial complex-I, complex-III, and complex-V, along with the glutathione and ATP contents, were significantly decreased in the liver of PEDV piglets. In contrast, the lipid peroxidation biomarkers, malondialdehyde, and ROS were markedly elevated. Moreover, we found that the peroxisome metabolism was inhibited by the PEDV infection using transcriptome analysis. These down-regulated anti-oxidative genes, including GPX4, CAT, SOD1, SOD2, GCLC, and SLC7A11, were further validated by qRT-PCR and immunoblotting. Because the nuclear receptor ROR\u03b3-driven MVA pathway is critical for LPO, we provided new evidence that ROR\u03b3 also controlled the genes CAT and GPX4 involved in peroxisome metabolism in the PEDV piglets. We found that ROR\u03b3 directly binds to these two genes using ChIP-seq and ChIP-qPCR analysis, where PEDV strongly repressed the binding enrichments. The occupancies of histone active marks such as H3K9\/27ac and H3K4me1\/2, together with active co-factor p300 and polymerase II at the locus of CAT and GPX4, were significantly decreased. Importantly, PEDV infection disrupted the physical association between ROR\u03b3 and NRF2, facilitating the down-regulation of the CAT and GPX4 genes at the transcriptional levels. ROR\u03b3 is a potential factor in modulating the CAT and GPX4 gene expressions in the liver of PEDV piglets by interacting with NRF2 and histone modifications.<\/jats:p>","DOI":"10.3390\/antiox12061305","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T01:37:38Z","timestamp":1687225058000},"page":"1305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hepatic Anti-Oxidative Genes CAT and GPX4 Are Epigenetically Modulated by ROR\u03b3\/NRF2 in Alphacoronavirus-Exposed Piglets"],"prefix":"10.3390","volume":"12","author":[{"given":"Haotian","family":"Gu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaya","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Qu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-2845","authenticated-orcid":false,"given":"Abdelkareem A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Darfur University College, Nyala 56022, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-1147","authenticated-orcid":false,"given":"Hao-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"International Joint Research Laboratory in Universities of Jiangsu Province of China for Domestic Animal Germplasm Resources and Genetic Improvement, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"International Joint Research Laboratory in Universities of Jiangsu Province of China for Domestic Animal Germplasm Resources and Genetic Improvement, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-5292","authenticated-orcid":false,"given":"Demin","family":"Cai","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"International Joint Research Laboratory in Universities of Jiangsu Province of China for Domestic Animal Germplasm Resources and Genetic Improvement, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.3201\/eid1212.060401","article-title":"Review of bats and SARS","volume":"12","author":"Wang","year":"2006","journal-title":"Emerg. 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