AUTHOR=Vasconez-Gonzalez Jorge , Suárez-Sangucho Isaac A. , Acosta-Muñoz Esteban , Miño Luis Paz y , Borja-Mendoza Domenic , Alexander-Castillo John Altamirano , Saa Julia , Salazar-Calvopiña Natasha , Cárdenas Paúl , López-Cortés Andrés , Ortiz-Prado Esteban 

TITLE=Human T-cell leukemia virus type 1: oncogenic potential and vaccine development strategies

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1587802

DOI=10.3389/fcimb.2025.1587802

ISSN=2235-2988

ABSTRACT=The human T-cell lymphotropic virus type 1 (HTLV-1) is a highly oncogenic retrovirus recognized as the causative agent of adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Among the key risk factors for ATLL development are high proviral load, reduced anti-Tax immune responses, and elevated levels of soluble interleukin-2 receptor. Unlike classical oncogenic viruses, HTLV-1 does not encode proto-oncogenes but instead drives cellular transformation through a combination of mechanisms, including viral gene dysregulation, chromatin remodeling, epigenetic reprogramming, persistent clonal expansion, immune evasion, and RNA-based modifications. Despite growing understanding of these molecular pathways, an effective prophylactic vaccine against HTLV-1 remains unavailable. However, several vaccine strategies including viral vector platforms, mRNA-based candidates, peptide vaccines, and dendritic cell-based approaches have shown promise in preclinical models. In this review, we provide a comprehensive synthesis of current knowledge on HTLV-1 oncogenesis, highlight the roles of viral proteins such as Tax and HBZ in immune evasion, and critically examine the state of vaccine development efforts aimed at controlling this neglected human retrovirus.