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Intestinal flora and its metabolites are important for the resistance of shrimp to lethal pathogenic viruses. However, the changes of metabolites in the shrimp intestines after WSSV infection remain unclear. We established an artificial oral infection method to infect shrimp with WSSV and analyzed the metabolites in intestinal content of shrimp by HPLC and tandem mass spectrometry. A total of 78 different metabolites and five different metabolic pathways were identified. Among them, we found that the content of linoleic acid, an unsaturated fatty acid, increased significantly after WSSV infection, indicating that linoleic acid might be involved in antiviral immunity in shrimp. Further study showed that, after oral administration of linoleic acid, WSSV proliferation decreased evidently in the shrimp, and survival rate of the shrimp increased significantly. Mechanical analysis showed that linoleic acid directly bound to WSSV virions and inhibited the viral replication. Linoleic acid also promoted the expression of antimicrobial peptides and IFN-like gene Vago5 by activating the ERK\u2013NF-\u03baB signaling pathway. Our results indicated that WSSV infection caused metabolomic transformation of intestinal microbiota and that the metabolite linoleic acid participated in the immune response against WSSV in shrimp.<\/jats:p>","DOI":"10.4049\/jimmunol.2001318","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T15:01:41Z","timestamp":1618585301000},"page":"2075-2087","source":"Crossref","is-referenced-by-count":32,"title":["Metabolomic Profiles in the Intestine of Shrimp Infected by White Spot Syndrome Virus and Antiviral Function of the Metabolite Linoleic Acid in Shrimp"],"prefix":"10.1093","volume":"206","author":[{"given":"Cang","family":"Li","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University , Qingdao, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chong","family":"Yang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University , Qingdao, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan-Pan","family":"Hong","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University , Qingdao, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University , Qingdao, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0283-3930","authenticated-orcid":false,"given":"Jin-Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University , Qingdao, Shandong ,","place":["China"]},{"name":"State Key Laboratory of Microbial Technology, Shandong University , Qingdao, Shandong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"2025030417503191800_r1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jip.2012.03.004","article-title":"Historic emergence, impact and current status of shrimp pathogens in Asia","volume":"110","author":"Flegel","year":"2012","journal-title":"J. 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