First Characterization of HTLV-1 Complete Genomes from Asymptomatic and Symptomatic Argentinean Patients

HTLV-1 is the etiologic agent of adult T-cell leukemia/lymphoma (ATL/ATLL) and is related to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The factors that influence the development of the disease remain unknown. The majority of patients with HTLV-1 infection remain asymptomatic throughout their lives, while 2.5%-5% developed ATLL and 0.3%-2% HAM/TSP. About 10 to 20 million people worldwide are infected with HTLV-1. In Argentina, HTLV-1 infection has been documented particularly in the northeast provinces neighboring Bolivia and Paraguay. This study aims to analyze the nine complete genomes of HTLV-1 from asymptomatic and symptomatic patients using next-generation sequencing. Mutation analysis and identification of viral integration sites were performed. Mutation analysis revealed distinct mutation patterns, identifying clusters associated with patients with HAM/TSP and lymphoma. Multiple integration sites across different chromosomes were found, suggesting random integration without specific hotspots. A defective provirus was identified in a patient with lymphoma, potentially impacting immune evasion and clonal expansion. Complete HTLV-1 genome sequences from circulating strains in Argentina were obtained for the first time. This contributes to the knowledge of the genetic variability of the virus and its integration sites in the human genome and reveals that the nature of the HTLV-1 provirus in natural infection is complex.