Sustained inflammation during human T-lymphotropic virus type 1 infection: a wildfire contributing to disease progression

Shegefti, Saina; Alaei, Mahsa; Ghahari, Nazanin; Telittchenko, Roman; Hanafi, s; Isnard, Stephane; Routy, Jean-Pierre; Olagnier, David et van Grevenynghe, Julien ORCID: https://orcid.org/0000-0002-2952-4081 (2025). Sustained inflammation during human T-lymphotropic virus type 1 infection: a wildfire contributing to disease progression Frontiers in Medicine , vol. 12 , nº 1653384. pp. 1-12. DOI: 10.3389/fmed.2025.1653384.

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Résumé

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus affecting 10-20 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-kappa B 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 "wildfire." 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 alpha/beta, IL-2, IL-6, IL-12, IL-17, TNF-alpha/beta, and IFN-gamma) and chemokines (MCP-1, MIP-1 alpha/beta, 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.

Type de document:	Article
Informations complémentaires:	This study was supported by the Canadian Institutes of Health Research (CIHR #486498)
Mots-clés libres:	ATLL; HAM-TSP; HTLV-1; HTLV-1 tax protein; NF-κB signaling pathway; asymptomatic carriers; cytokine/chemokine; inflammation
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	16 juin 2026 14:50
Dernière modification:	16 juin 2026 14:50
URI:	https://espace.inrs.ca/id/eprint/16691

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