{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:50:09Z","timestamp":1768611009361,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon Europe research and innovation programme","award":["101079467"],"award-info":[{"award-number":["101079467"]}]},{"name":"FCT, Portugal","award":["2021.04867.BD"],"award-info":[{"award-number":["2021.04867.BD"]}]},{"name":"FCT, Portugal","award":["2020.00290.CEECIND"],"award-info":[{"award-number":["2020.00290.CEECIND"]}]},{"name":"FCT, Portugal","award":["2022.03304.CEECIND"],"award-info":[{"award-number":["2022.03304.CEECIND"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Several studies have demonstrated that methionine supplementation in fish diets enhances immune status, inflammatory response, and resistance to bacterial infections by modulating for DNA methylation, aminopropylation, and transsulfuration pathways. However, the immunomodulatory effects of methionine in viral infections remain unexplored. This study aimed to evaluate the effect of methionine supplementation on immune modulation and resistance to the viral haemorrhagic septicaemia virus (VHSV) in rainbow trout (Oncorhynchus mykiss). Two diets were formulated and fed to juvenile rainbow trout for four weeks: a control diet (CTRL) with all nutritional requirements, including the amino acid profile required for the species, and a methionine-supplemented diet (MET), containing twice the normal requirement of DL-methionine. After feeding, fish were bath-infected with VHSV, while control fish were exposed to a virus-free bath. Samples were collected at 0 (after feeding trial), 24, 72, and 120 h post-infection for the haematological profile, humoral immune response, oxidative stress, viral load, RNAseq, and gene expression analysis. In both diets, results showed a peak in viral activity at 72 h, followed by a reduction in viral load at 120 h, indicating immune recovery. During the peak of infection, leukocytes, thrombocytes, and monocytes migrated to the infection site, while oxidative stress biomarkers (superoxide dismutase glutathione S-transferase, and glutathione redox ratio) suggested a compromised ability to manage cellular imbalance due to intense viral activity. At 120 h, immune recovery and homeostasis were observed due to an increase in the amount of nitric oxide, GSH\/GSSG levels, leukocyte replacement, monocyte influx, and a reduction in the viral load. When focusing on the infection peak, gene ontology (GO) analysis showed several exclusively enriched pathways in the skin and gills of MET-fed fish, driven by the upregulation of several key genes. Genes involved in recognition\/signalling, inflammatory response, and other genes with direct antiviral activity, such as TLR3, MYD88, TRAF2, NF-\u03baB, STING, IRF3, -7, VIG1, caspases, cathepsins, and TNF, were observed. Notably, VIG1 (viperin), a key antiviral protein, was significantly upregulated in gills, confirming the modulatory role of methionine in inducing its transcription. Viperin, which harbours an S-adenosyl-L-methionine (SAM) radical domain, is directly related to methionine biosynthesis and plays a critical role in the innate immune response to VHSV infection in rainbow trout. In summary, this study suggests that dietary methionine supplementation can enhance a more robust fish immune response to viral infections, with viperin as a crucial mediator. The improved antiviral readiness observed in MET-fed fish underscores the potential of targeted nutritional adjustments to sustain fish health and welfare in aquaculture.<\/jats:p>","DOI":"10.3390\/biology15020163","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:27:53Z","timestamp":1768570073000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dietary Methionine Supplementation Improves Rainbow Trout (Oncorhynchus mykiss) Immune Responses Against Viral Haemorrhagic Septicaemia Virus (VHSV)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6064-0227","authenticated-orcid":false,"given":"Mariana","family":"Vaz","sequence":"first","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Porto, Portugal"},{"name":"Faculty of Mathematics and Natural Sciences, University of Bergen, 5007 Bergen, Norway"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-9439","authenticated-orcid":false,"given":"Gon\u00e7alo Espregueira","family":"Themudo","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-2650","authenticated-orcid":false,"given":"In\u00eas","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS-UP), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-0330","authenticated-orcid":false,"given":"Felipe Bolgenhagen","family":"Sch\u00f6ninger","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0860-2976","authenticated-orcid":false,"given":"Carolina","family":"Tafalla","sequence":"additional","affiliation":[{"name":"Fish Immunology and Pathology Group, Biotechnology Department, National Institute for Agricultural and Food Research and Technology (INIA), Spanish National Research Council (CSIC), Carretera de La Coru\u00f1a km 7.5, 28040 Madrid, Spain"}]},{"given":"Patricia","family":"D\u00edaz-Rosales","sequence":"additional","affiliation":[{"name":"Fish Immunology and Pathology Group, Biotechnology Department, National Institute for Agricultural and Food Research and Technology (INIA), Spanish National Research Council (CSIC), Carretera de La Coru\u00f1a km 7.5, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-0849","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Costas","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS-UP), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7718-5021","authenticated-orcid":false,"given":"Marina","family":"Machado","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00726-009-0269-0","article-title":"Amino acids: Metabolism, functions, and nutrition","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.fsi.2014.11.024","article-title":"Dietary tryptophan and methionine as modulators of European seabass (Dicentrarchus labrax) immune status and inflammatory response","volume":"42","author":"Machado","year":"2015","journal-title":"Fish Shellfish Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Azeredo, R., Machado, M., Afonso, A., Fierro-Castro, C., Reyes-L\u00f3pez, F.E., Tort, L., Gesto, M., Conde-Sieira, M., M\u00edguez, J.M., and Soengas, J.L. (2017). Neuroendocrine and Immune Responses Undertake Different Fates following Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01226"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1017\/S0007114520001877","article-title":"Dietary methionine supplementation improves the European seabass (Dicentrarchus labrax) immune status following long-term feeding on fishmeal-free diets","volume":"124","author":"Machado","year":"2020","journal-title":"Br. J. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113690","DOI":"10.1016\/j.ygcen.2020.113690","article-title":"Dietary methionine as a strategy to improve innate immunity in rainbow trout (Oncorhynchus mykiss) juveniles","volume":"302","author":"Machado","year":"2021","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e12891","DOI":"10.1111\/cpr.12891","article-title":"S-adenosylmethionine: A metabolite critical to the regulation of autophagy","volume":"53","author":"Ouyang","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/bse0460003","article-title":"S-Adenosylmethionine decarboxylase","volume":"46","author":"Pegg","year":"2009","journal-title":"Essays Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Machado, M., Azeredo, R., Fontinha, F., Fern\u00e1ndez-Boo, S., Concei\u00e7\u00e3o, L.E.C., Dias, J., and Costas, B. (2018). Dietary Methionine Improves the European Seabass (Dicentrarchus labrax) Immune Status, Inflammatory Response, and Disease Resistance. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02672"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.aquaculture.2017.06.017","article-title":"Effects of dietary methionine and taurine supplementation to low-fish meal diets on growth performance and oxidative status of European sea bass (Dicentrarchus labrax) juveniles","volume":"479","author":"Coutinho","year":"2017","journal-title":"Aquaculture"},{"key":"ref_10","first-page":"e13180","article-title":"Rice protein stimulates endogenous antioxidant response attributed to methionine availability in growing rats","volume":"44","author":"Wang","year":"2020","journal-title":"J. Food Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"740013","DOI":"10.1016\/j.aquaculture.2023.740013","article-title":"Methionine deficiency affects myogenesis and muscle macronutrient metabolism in juvenile turbot Scophthalmus maximus","volume":"578","author":"Sui","year":"2024","journal-title":"Aquaculture"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1093\/jn\/112.8.1525","article-title":"Methionine Metabolism in Rainbow Trout Fed Diets of Differing Methionine and Cystine Content","volume":"112","author":"Walton","year":"1982","journal-title":"J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1093\/jn\/122.5.1154","article-title":"Methionine Intake in Rainbow Trout (Oncorhynchus mykiss), Relationship to Cataract Formation and the Metabolism of Methionine","volume":"122","author":"Cowey","year":"1992","journal-title":"J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1365-2761.2005.00654.x","article-title":"Viral haemorrhagic septicaemia virus in marine fish and its implications for fish farming\u2014A review","volume":"28","author":"Skall","year":"2005","journal-title":"J. Fish Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1099\/vir.0.048223-0","article-title":"Inter-species transmission of viral hemorrhagic septicemia virus (VHSV) from turbot (Scophthalmus maximus) to rainbow trout (Onchorhynchus mykiss)","volume":"94","author":"Lorenzen","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114639","DOI":"10.1016\/j.jviromet.2022.114639","article-title":"Development of rapid neutralization assay of viral hemorrhagic septicemia virus (VHSV) based on chimeric rhabdovirus expressing heterologous glycoprotein","volume":"311","author":"Lee","year":"2023","journal-title":"J. Virol. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1099\/vir.0.79820-0","article-title":"Evolution of the fish rhabdovirus viral haemorrhagic septicaemia virus","volume":"85","author":"Ahrens","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108456","DOI":"10.1016\/j.fsi.2022.108456","article-title":"In vitro and in vivo evaluation of the antiviral activity of arctigenin, ribavirin, and ivermectin against viral hemorrhagic septicemia virus infection","volume":"132","author":"Baek","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108617","DOI":"10.1016\/j.fsi.2023.108617","article-title":"Effect of temperature and IRF-9 gene-knockout on dynamics of vRNA, cRNA, and mRNA of viral hemorrhagic septicemia virus (VHSV)","volume":"134","author":"Lee","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.fsi.2020.05.038","article-title":"IRF9 promotes apoptosis and innate immunity by inhibiting SIRT1-p53 axis in fish","volume":"103","author":"Jiang","year":"2020","journal-title":"Fish Shellfish Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ortega-Villaizan, M.d.M., Chico, V., and Perez, L. (2022). Fish Innate Immune Response to Viral Infection\u2014An Overview of Five Major Antiviral Genes. Viruses, 14.","DOI":"10.3389\/fimmu.2023.1155538"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vaz, M., Themudo, G.E., Sch\u00f6ninger, F.B., Carvalho, I., Tafalla, C., D\u00edaz-Rosales, P., Ramos-Pinto, L., Costas, B., and Machado, M. (2025). Unraveling the Systemic and Local Immune Response of Rainbow Trout (Oncorhynchus mykiss) to the Viral Hemorrhagic Septicemic Virus. Biology, 14.","DOI":"10.3390\/biology14081003"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1053\/j.gastro.2010.09.010","article-title":"S-Adenosyl Methionine Improves Early Viral Responses and Interferon-Stimulated Gene Induction in Hepatitis C Nonresponders","volume":"140","author":"Feld","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/anu.12233","article-title":"Review on European sea bass (Dicentrarchus labrax, Linnaeus, 1758) nutrition and feed management: A practical guide for optimizing feed formulation and farming protocols","volume":"21","author":"Kousoulaki","year":"2015","journal-title":"Aquac. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fimmu.2025.1706922","article-title":"Immunomodulatory effects of dietary methionine supplementation in rainbow trout (Oncorhynchus mykiss) juveniles: Insights following vaccination and infection response against Yersinia ruckeri","volume":"16","author":"Carvalho","year":"2025","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1182\/blood.V26.2.215.215","article-title":"Brief Report: Simplified Myeloperoxidase Stain Using Benzidine Dihydrochloride","volume":"26","author":"Kaplow","year":"1965","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3354\/dao034027","article-title":"Neutrophil and macrophage responses to inflammation in the peritoneal cavity of rainbow trout Oncorhynchus mykiss. A light and electron microscopic cytochemical study","volume":"34","author":"Afonso","year":"1998","journal-title":"Dis. Aquat. Org."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Peixoto, D., Carvalho, I., Cunha, A., Santos, P., Ramos-Pinto, L., Machado, M., Azeredo, R., and Costas, B. (2024). Synergistic Effects of Dietary Tryptophan and Dip Vaccination in the Immune Response of European Seabass Juveniles. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212200"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1016\/S0021-9258(19)42083-8","article-title":"Glutathione S-transferases. The first enzymatic step in mercapturic acid formation","volume":"249","author":"Habig","year":"1974","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1023\/A:1025457831923","article-title":"Effects of dimethoate and beta-naphthoflavone on selected biomarkers of Poecilia reticulata","volume":"26","author":"Frasco","year":"2002","journal-title":"Fish Physiol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.freeradbiomed.2014.05.017","article-title":"Ontogeny of redox regulation in Atlantic cod (Gadus morhua) larvae","volume":"73","author":"Hamre","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/0003-2697(69)90064-5","article-title":"Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues","volume":"27","author":"Tietze","year":"1969","journal-title":"Anal. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jviromet.2005.10.005","article-title":"Rapid detection and quantitation of viral hemorrhagic septicemia virus in experimentally challenged rainbow trout by real-time RT-PCR","volume":"132","author":"Chico","year":"2006","journal-title":"J. Virol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Langevin, C., Blanco, M., Martin, S.A.M., Jouneau, L., Bernardet, J.-F., Houel, A., Lunazzi, A., Duchaud, E., Michel, C., and Quillet, E. (2012). Transcriptional Responses of Resistant and Susceptible Fish Clones to the Bacterial Pathogen Flavobacterium psychrophilum. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039126"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1128\/CVI.00404-13","article-title":"Insight from Molecular, Pathological, and Immunohistochemical Studies on Cellular and Humoral Mechanisms Responsible for Vaccine-Induced Protection of Rainbow Trout Against Yersinia ruckeri","volume":"20","author":"Deshmukh","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1365-2095.2008.00613.x","article-title":"Effect of methionine on intestinal enzymes activities, microflora and humoral immune of juvenile Jian carp (Cyprinus carpio var. Jian)","volume":"15","author":"Tang","year":"2009","journal-title":"Aquac. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3354\/dao02344","article-title":"Development and validation of a reverse transcription quantitative PCR for universal detection of viral hemorrhagic septicemia virus","volume":"95","author":"Garver","year":"2011","journal-title":"Dis. Aquat. Org."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2478\/jvetres-2019-0017","article-title":"Characterisation of thrombocytes in Osteichthyes","volume":"63","author":"Stosik","year":"2019","journal-title":"J. Vet. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Vaz, M., Pires, D., Pires, P., Sim\u00f5es, M., Pombo, A., Santos, P., do Carmo, B., Passos, R., Costa, J.Z., and Thompson, K.D. (2022). Early Immune Modulation in European Seabass (Dicentrarchus labrax) Juveniles in Response to Betanodavirus Infection. Fishes, 7.","DOI":"10.3390\/fishes7020063"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chico, V., Salvador-Mira, M.E., Nombela, I., Puente-Marin, S., Ciordia, S., Mena, M.C., Perez, L., Coll, J., Guzman, F., and Encinar, J.A. (2019). IFIT5 Participates in the Antiviral Mechanisms of Rainbow Trout Red Blood Cells. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00613"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ortega-Villaizan, M.D.M., Coll, J., and Rimstad, E. (2022). Editorial: The role of red blood cells in the immune response of fish. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1005546"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.fsi.2018.09.042","article-title":"Distinct \u03b2-glucan molecules modulates differently the circulating cortisol levels and innate immune responses in matrinx\u00e3 (Brycon amazonicus)","volume":"83","author":"Favero","year":"2018","journal-title":"Fish Shellfish Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ecolind.2012.04.009","article-title":"Effect of temperature on oxidative stress in fish: Lipid peroxidation and catalase activity in the muscle of juvenile seabass, Dicentrarchus labrax","volume":"23","author":"Vinagre","year":"2012","journal-title":"Ecol. Indic."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpc.2016.07.007","article-title":"Effects of stocking density on antioxidant status, metabolism and immune response in juvenile turbot (Scophthalmus maximus)","volume":"190","author":"Liu","year":"2016","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.fsi.2019.04.036","article-title":"Effect of symbiotic supplemented diet on innate-adaptive immune response, cytokine gene regulation and antioxidant property in Labeo rohita against Aeromonas hydrophila","volume":"89","author":"Devi","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2003895","DOI":"10.1002\/advs.202003895","article-title":"Nitric Oxide to Fight Viral Infections","volume":"8","author":"Lisi","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1546-5098(08)60272-1","article-title":"The Nonspecific Immune System: Cellular Defenses","volume":"Volume 15","author":"Iwama","year":"1996","journal-title":"Fish Physiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0165-2427(99)00109-9","article-title":"Role of nitric oxide on the replication of viral haemorrhagic septicemia virus (VHSV), a fish rhabdovirus","volume":"72","author":"Tafalla","year":"1999","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1128\/JVI.72.3.2538-2540.1998","article-title":"Effect of Nitric Oxide on Poliovirus Infection of Two Human Cell Lines","volume":"72","author":"Carrasco","year":"1998","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ferreira, I.A., Santos, P., Mox\u00f3, J.S., Teixeira, C., do Vale, A., and Costas, B. (2024). Tenacibaculum maritimum can boost inflammation in Dicentrarchus labrax upon peritoneal injection but cannot trigger tenacibaculosis disease. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1478241"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"108848","DOI":"10.1016\/j.cbpc.2020.108848","article-title":"Rutin-added diet protects silver catfish liver against oxytetracycline-induced oxidative stress and apoptosis","volume":"239","author":"Londero","year":"2021","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.fsi.2016.05.032","article-title":"Stress and immune responses in skin of turbot (Scophthalmus maximus) under different stocking densities","volume":"55","author":"Jia","year":"2016","journal-title":"Fish Shellfish Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0147-6513(03)00009-5","article-title":"Oxidative stress biomarkers of exposure to deltamethrin in freshwater fish, Channa punctatus Bloch","volume":"56","author":"Sayeed","year":"2003","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0076-6879(90)86135-I","article-title":"Malondialdehyde determination as index of lipid Peroxidation","volume":"Volume 186","author":"Draper","year":"1990","journal-title":"Methods in Enzymology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Anderson, M., Punchard, N.A., and Kelly, F.J. (1996). Glutathione. Free Radicals: A Practical Approach, Oxford University Press.","DOI":"10.1093\/oso\/9780199635603.001.0001"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.fsi.2019.03.073","article-title":"Interferon-regulatory factors, IRF3 and IRF7 in Asian seabass, Lates calcarifer: Characterization, ontogeny and transcriptional modulation upon challenge with nervous necrosis virus","volume":"89","author":"Krishnan","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7573","DOI":"10.4049\/jimmunol.1002401","article-title":"Characterization of Fish IRF3 as an IFN-Inducible Protein Reveals Evolving Regulation of IFN Response in Vertebrates","volume":"185","author":"Sun","year":"2010","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.fsi.2010.02.017","article-title":"Probiotics and immunity: A fish perspective","volume":"29","author":"Nayak","year":"2010","journal-title":"Fish Shellfish Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1006\/fsim.1999.0194","article-title":"Immunity to rhabdoviruses in rainbow trout: The antibody response","volume":"9","author":"Lorenzen","year":"1999","journal-title":"Fish Shellfish Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/aah.10068","article-title":"Differences of Viral Hemorrhagic Septicemia Virus Loads among Organs of Dead and Surviving Olive Flounder Infected by Intramuscular Injection and Immersion Challenge","volume":"31","author":"Kim","year":"2019","journal-title":"J. Aquat. Anim. Health"},{"key":"ref_63","first-page":"853470","article-title":"An Overview of the Immunological Defenses in Fish Skin","volume":"2012","year":"2012","journal-title":"Int. Sch. Res. Not."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Carvalho, I., Peixoto, D., Ferreira, I., Robledo, D., Ramos-Pinto, L., Silva, R.M., Gon\u00e7alves, J.F., Machado, M., Tafalla, C., and Costas, B. (2025). Exploring the effects of dietary methionine supplementation on European seabass mucosal immune responses against Tenacibaculum maritimum. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1513516"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"101473","DOI":"10.1016\/j.aqrep.2023.101473","article-title":"Dynamic immune response in the spleens of rainbow trout (Oncorhynchus mykiss) to infectious hematopoietic necrosis virus revealed by transcriptome and immune-related genes expression analysis","volume":"29","author":"Pan","year":"2023","journal-title":"Aquac. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.fsi.2015.10.039","article-title":"Fish IRF3 up-regulates the transcriptional level of IRF1, IRF2, IRF3 and IRF7 in CIK cells","volume":"47","author":"Xu","year":"2015","journal-title":"Fish Shellfish Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"198525","DOI":"10.1016\/j.virusres.2021.198525","article-title":"Novirhabdoviruses versus fish innate immunity: A review","volume":"304","author":"He","year":"2021","journal-title":"Virus Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.cyto.2008.07.010","article-title":"Signalling adaptors used by Toll-like receptors: An update","volume":"43","author":"Kenny","year":"2008","journal-title":"Cytokine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yexcr.2017.02.035","article-title":"Innate immune receptors in skeletal muscle metabolism","volume":"360","author":"Pillon","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.it.2016.12.004","article-title":"Crosstalk Between Cytoplasmic RIG-I and STING Sensing Pathways","volume":"38","author":"Zevini","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4904","DOI":"10.1016\/j.jmb.2013.09.033","article-title":"The Antiviral Innate Immune Response in Fish: Evolution and Conservation of the IFN System","volume":"425","author":"Langevin","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"14309","DOI":"10.1074\/jbc.M708895200","article-title":"The Role of TRAF2 Binding to the Type I Interferon Receptor in Alternative NF\u03baB Activation and Antiviral Response","volume":"283","author":"Yang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103781","DOI":"10.1016\/j.dci.2020.103781","article-title":"Grass carp (Ctenopharyngodon idella) GPATCH3 initiates IFN 1 expression via the activation of STING-IRF7 signal axis","volume":"112","author":"Li","year":"2020","journal-title":"Dev. Comp. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.fsi.2020.04.021","article-title":"Fish TRAF2 promotes innate immune response to RGNNV infection","volume":"102","author":"Li","year":"2020","journal-title":"Fish Shellfish Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrmicro2539","article-title":"Modulation of NF-\u03baB signalling by microbial pathogens","volume":"9","author":"Rahman","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41576-019-0151-1","article-title":"DNA sensing by the cGAS\u2013STING pathway in health and disease","volume":"20","author":"Motwani","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"E2058","DOI":"10.1073\/pnas.1716937115","article-title":"STING-dependent translation inhibition restricts RNA virus replication","volume":"115","author":"Franz","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/JLB.2MIR0917-383R","article-title":"On taking the STING out of immune activation","volume":"103","author":"Banete","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"310","DOI":"10.4049\/jimmunol.1501836","article-title":"A cGAS-Independent STING\/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines","volume":"196","author":"Suschak","year":"2016","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.dci.2014.03.001","article-title":"Identification, characterization and immunological response analysis of stimulator of interferon gene (STING) from grass carp Ctenopharyngodon idella","volume":"45","author":"Feng","year":"2014","journal-title":"Dev. Comp. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109098","DOI":"10.1016\/j.fsi.2023.109098","article-title":"Molecular and functional characterization of viperin in golden pompano, Trachinotus ovatus","volume":"142","author":"Huang","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.4049\/jimmunol.177.8.5059","article-title":"Involvement of the I\u03baB Kinase (IKK)-Related Kinases Tank-Binding Kinase 1\/IKKi and Cullin-Based Ubiquitin Ligases in IFN Regulatory Factor-3 Degradation1","volume":"177","author":"Gravel","year":"2006","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11079","DOI":"10.1128\/JVI.05098-11","article-title":"Varicella-Zoster Virus Immediate-Early Protein ORF61 Abrogates the IRF3-Mediated Innate Immune Response Through Degradation of Activated IRF3","volume":"85","author":"Zhu","year":"2011","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6806","DOI":"10.1073\/pnas.1705402114","article-title":"Structural studies of viperin, an antiviral radical SAM enzyme","volume":"114","author":"Fenwick","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-virology-011720-095930","article-title":"Viperin Reveals Its True Function","volume":"7","author":"Gizzi","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.dci.2017.10.013","article-title":"Molecular characterization and expression analyses of the Viperin gene in Larimichthys crocea (Family: Sciaenidae)","volume":"79","author":"Zhang","year":"2018","journal-title":"Dev. Comp. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1665-2681(19)31355-9","article-title":"S-adenosylmethionine metabolism and liver disease","volume":"12","author":"Mato","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"110699","DOI":"10.1016\/j.cbpb.2021.110699","article-title":"Molecular characterization, expression profile, and antiviral activity of redlip mullet (Liza haematocheila) viperin","volume":"258","author":"Madushani","year":"2022","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.fsi.2022.10.040","article-title":"Generation of viperin-knockout zebrafish by CRISPR\/Cas9-mediated genome engineering and the effect of this mutation under VHSV infection","volume":"131","author":"Shanaka","year":"2022","journal-title":"Fish Shellfish Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.fsi.2020.07.047","article-title":"Identification and functional characterization of three caspases in Takifugu obscurus in response to bacterial infection","volume":"106","author":"Fu","year":"2020","journal-title":"Fish Shellfish Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Scarcella, M., d\u2019Angelo, D., Ciampa, M., Tafuri, S., Avallone, L., Pavone, L.M., and De Pasquale, V. (2022). The Key Role of Lysosomal Protease Cathepsins in Viral Infections. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169089"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/2\/163\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:39:55Z","timestamp":1768570795000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/2\/163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":91,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["biology15020163"],"URL":"https:\/\/doi.org\/10.3390\/biology15020163","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}