{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:06:29Z","timestamp":1779271589054,"version":"3.51.4"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alterations in the immune response may influence the development of HTLV-1-associated diseases. TLR3 detects viral nucleic acids, including HTLV-1, and triggers the production of IFN-I and other cytokines. Genetic variations in <jats:italic>TLR3<\/jats:italic> may alter the antiviral and inflammatory responses and contribute to the progression of HTLV-1 infection. The present study investigated the association of polymorphisms in the <jats:italic>TLR3<\/jats:italic> gene (rs5743305 T\/A and rs3775291 C\/T) with HTLV-1 infection status and their relationship with infection-associated diseases, receptor expression levels, proviral load, and inflammatory and antiviral cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood samples were collected from 179 individuals with HTLV-1 infection (82 with inflammatory diseases and 97 asymptomatic individuals) and 179 controls. Genotyping of polymorphisms, analysis of <jats:italic>TLR3<\/jats:italic> gene expression, and quantification of proviral load were performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The polymorphisms showed no correlation with susceptibility to HTLV-1 infection, or the occurrence of disease symptoms linked to the infection. The presence of disease symptoms was associated with higher TNF-\u03b1 levels and proviral load. <jats:italic>TLR3<\/jats:italic> rs5743305 T\/A polymorphism was not associated with variations in <jats:italic>TLR3<\/jats:italic> and IFN-\u03b1 levels. For the <jats:italic>TLR3<\/jats:italic> rs3775291 C\/T polymorphism, asymptomatic individuals carrying the TT polymorphic genotype presented significantly higher IFN-\u03b1 levels and lower proviral load. The profile of asymptomatic individuals carrying the polymorphic genotypes for <jats:italic>TLR3<\/jats:italic> rs3775291 C\/T was characterized by higher levels of <jats:italic>TLR3<\/jats:italic> and IFN-\u03b1 and lower levels of proviral load, TNF-\u03b1 and IL-6 compared to those with the wild-type genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although polymorphisms in the TLR3 gene have not been associated with the presence of symptoms of HTLV-1-related inflammatory diseases, the <jats:italic>TLR3<\/jats:italic> rs3775291 C\/T polymorphism appears to contribute to a better evolution of the HTLV-1 infection status and inflammatory process among asymptomatic individuals.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1604259","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T05:26:15Z","timestamp":1754285175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["TLR3 rs3775291 C\/T polymorphism is associated with elevated IFN-\u03b1 level in asymptomatic HTLV-1 infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Fabiane dos Santos","family":"Ferreira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wandrey Roberto dos Santos","family":"Brito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle Giuliana Mendes","family":"Santana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Kelly Alves","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Cecy Rocha de","family":"Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ednelza da Silva Gra\u00e7a","family":"Amoras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Araujo","family":"da Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u00edsa Silva","family":"Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra Souza","family":"Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Ishak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izaura Maria Vieira","family":"Cayres-Vallinoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Carlos Ros\u00e1rio","family":"Vallinoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Alice Freitas","family":"Queiroz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat. 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