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Immunol."],"abstract":"<jats:p>Virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains, such as the Lena strain, have demonstrated a higher thymus tropism than low virulent strains. Virulent PRRSV strains lead to severe thymus atrophy, which could be related to marked immune dysregulation. Impairment of T-cell functions through immune checkpoints has been postulated as a strategy executed by PRRSV to subvert the immune response, however, its role in the thymus, a primary lymphoid organ, has not been studied yet. Therefore, the goal of this study was to evaluate the expression of selected immune checkpoints (<jats:italic>PD1\/PDL1, CTLA4, TIM3, LAG3, CD200R1<\/jats:italic> and <jats:italic>IDO1<\/jats:italic>) in the thymus of piglets infected with two different PRRSV-1 strains. Thymus samples from piglets infected with the low virulent 3249 strain, the virulent Lena strain and mock-infected were collected at 1, 3, 6, 8 and 13 days post-infection (dpi) to analyze PRRSV viral load, relative quantification and immunohistochemical staining of immune checkpoints. <jats:italic>PD1\/PDL1<\/jats:italic>, <jats:italic>CTLA4<\/jats:italic>, <jats:italic>TIM3<\/jats:italic>, <jats:italic>LAG3<\/jats:italic> and <jats:italic>IDO1<\/jats:italic> immune checkpoints were significantly up-regulated in the thymus of PRRSV infected piglets, especially in those infected with the virulent Lena strain from 6 dpi onwards. This up-regulation was associated with disease progression, high viral load and cell death. Co-expression of these molecules can affect T-cell development, maturation and selection, negatively regulating the host immune response against PRRSV.<\/jats:p>","DOI":"10.3389\/fimmu.2021.671743","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T07:01:14Z","timestamp":1620716474000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion"],"prefix":"10.3389","volume":"12","author":[{"given":"In\u00e9s","family":"Ruedas-Torres","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.","family":"Rodr\u00edguez-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 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