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Although arginine (Arg) is known to support the integrity of intestinal barrier, it is not clear whether Arg can alleviate intestinal injury induced by PEDV. A total of 32 healthy 7-day-old piglets were randomly assigned to four groups (Control, Arg, PEDV, PEDV + Arg; eight replicates per group). From day 5, piglets in the Arg and PEDV + Arg groups were orally administered Arg at 400 mg\/kg body weight until day 11; then, PEDV (1 \u00d7 105.5 TCID50) was given orally for two PEDV-infected groups. On day 14, all piglets were slaughtered to obtain blood and intestine samples for further analysis. The results showed that PEDV infection significantly reduced T-SOD and CAT activities in plasma and intestine while elevating MPO levels. Arg supplementation restored T-SOD (plasma, duodenum, ileum), CAT (plasma, ileum), and GSH-Px (jejunum, ileum) activities and reduced MDA (jejunum) content in PEDV-infected piglets. Hematological analysis showed Arg alleviated PEDV-induced increases in MCV and RDW-SD, and significantly elevated MCHC. The real-time quantitative PCR analysis demonstrated that Arg further enhanced PEDV structural genes (M, N, S) expression in the duodenum, ileum, and colon. Concurrently, Arg significantly up-regulated interferon-stimulated genes (MX1, OASL, ISG15, IFITM3) in the ileum, IRF7 in the duodenum and colon, and IFN-\u03b2 in the ileum. Arg also down-regulated the pro-inflammatory cytokines IL-6 and CXCL2 and the antimicrobial peptide REG3G in the colon, while up-regulating the tissue repair gene MMP13 in the ileum. In conclusion, oral Arg exhibits a unique dual role: it promotes PEDV replication to a certain extent while significantly enhancing antioxidant capacity, strengthening intestinal antiviral immunity, and attenuating intestinal inflammation. These findings highlight Arg\u2019s role in promoting disease tolerance and offer a novel perspective for nutritional intervention strategies against PEDV infection.<\/jats:p>","DOI":"10.3390\/ani16132002","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"2002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Arginine Supplementation on Intestinal Antioxidant Capacity, Whole Blood Cell Count and Antiviral Immune Function of Piglets Infected with Porcine Epidemic Diarrhea Virus"],"prefix":"10.3390","volume":"16","author":[{"given":"Zhiwei","family":"Zhang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Du","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Jian","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbo","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0790-6884","authenticated-orcid":false,"given":"Zhonghua","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-2931","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yi","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"},{"name":"Engineering Research Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and 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Center of Feed Protein Resources of Agricultural By-Products, Ministry of Education, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/tbed.12823","article-title":"Swine enteric coronavirus disease: A review of 4 years with porcine epidemic diarrhoea virus and porcine deltacoronavirus in the United States and Canada","volume":"65","author":"Niederwerder","year":"2018","journal-title":"Transbound. 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