Human T-cell Leukemia Virus Type 1 (HTLV-1): Oncogenic Potential and Vaccine Development Strategies

Jorge Vasconez-Gonzalez¹Isaac A. Suarez Sangucho¹Esteban Acosta Muñoz¹Luis Paz Y Miño¹Domenic Borja-Mendoza¹John Altamirano Alexander-Castillo¹Julia Saa¹Natasha Salazar-Calvopiña¹Paul Cardenas²Andrés López-Cortés¹Esteban Ortiz-Prado^1*

• ¹University of the Americas, Quito, Ecuador
• ²Universidad San Francisco de Quito, Quito, Pichincha, Ecuador

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.