{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:12:59Z","timestamp":1791213179221,"version":"4.1.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus affecting 10\u201320 million people worldwide. While many carriers remain asymptomatic, HTLV-1 infection can trigger intense inflammatory responses which are defined by the sustained release of pro-inflammatory cytokines and chemokines. Central to this process is the HTLV-1 encoded Tax oncoprotein, a viral regulator that drives uncontrolled inflammation by hijacking multiple cellular signaling pathways, such as the RelA\/NF-\u03baB signal transduction pathway. CD4 T-cells are the primary targets of Tax-mediated transformation, undergoing uncontrolled proliferation and significantly contributing to chronic immune activation seen in HTLV-1-associated diseases. However, highly activated CD4 T-cells are not alone in fueling this inflammatory \u201cwildfire.\u201d Other immune cells, including CD8 T-cells, monocytes, macrophages, dendritic cells, and neutrophils, also play critical roles in exacerbating the inflammatory milieu. These cells, in conjunction with CD4 T-cells, release a barrage of pro-inflammatory cytokines (IL-1\u03b1\/\u03b2, IL-2, IL-6, IL-12, IL-17, TNF-\u03b1\/\u03b2, and IFN-\u03b3) and chemokines (MCP-1, MIP-1\u03b1\/\u03b2, RANTES, MCP-3, IL-8, CXCL9, CXCL10, and CXCL11), all of which are perpetuating the cycle of immune activation and tissue damage. This hyper stimulated immune response contributes to HTLV-1 replication\/dissemination and can lead to the development of adult T-cell leukemia\/lymphoma (ATLL) and HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM-TSP). Despite existing treatments aimed at controlling viral replication, the persistent inflammation in HTLV-1-infected individuals even in asymptomatic carriers (ACs) remains a major challenge, suggesting that targeting these pro-inflammatory responses may be another mandatory therapeutic strategy. In this context, this short-review focuses on the key immune responses that drive HTLV-1-associated inflammation and explores how these high pro-inflammatory responses contribute to the development of HTLV-1-related complications, including HAM-TSP, ATLL, and other associated inflammatory diseases during chronic viral infection.<\/jats:p>","DOI":"10.3389\/fmed.2025.1653384","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:37:24Z","timestamp":1757655444000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Sustained inflammation during human T-lymphotropic virus type 1 infection: a wildfire contributing to disease progression"],"prefix":"10.3389","volume":"12","author":[{"given":"Saina","family":"Shegefti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Alaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazanin","family":"Ghahari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Telittchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin 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