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Type I interferon has been successfully used for treating some chronic viral infections in humans. However, its application in salmonids depends on the proper design of a vehicle that allows its massive administration, ideally orally. In mammals, administration of recombinant probiotics capable of expressing cytokines has shown local and systemic therapeutic effects. In this work, we evaluate the use of <jats:italic>Lactococcus lactis<\/jats:italic> as a type I Interferon expression system in Atlantic salmon, and we analyze its ability to stimulate the antiviral immune response against IPNV, <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. The interferon expressed in <jats:italic>L. lactis<\/jats:italic>, even though it was located mainly in the bacterial cytoplasm, was functional, stimulating Mx and PKR expression in CHSE-214 cells, and reducing the IPNV viral load in SHK-1 cells. <jats:italic>In vivo<\/jats:italic>, the oral administration of this <jats:italic>L. lactis<\/jats:italic> producer of Interferon I increases Mx and PKR expression, mainly in the spleen, and to a lesser extent, in the head kidney. The oral administration of this strain also reduces the IPNV viral load in Atlantic salmon specimens challenged with this pathogen. Our results show that oral administration of <jats:italic>L. lactis<\/jats:italic> producing Interferon I induces systemic effects in Atlantic salmon, allowing to stimulate the antiviral immune response. This probiotic could have effects against a wide variety of viruses that infect Atlantic salmon and also be effective in other salmonids due to the high identity among their type I interferons.<\/jats:p>","DOI":"10.3389\/fimmu.2021.696781","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:10:20Z","timestamp":1628763020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Lactococcus lactis Expressing Type I Interferon From Atlantic Salmon Enhances the Innate Antiviral Immune Response In Vivo and In 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