Pineda María Verónica, Miyazato Paola, Distefano Maximiliano, Tan Jek Yang Benjy, Golemba Marcelo, Bouzas María Belén, Satou Yorifumi, Mangano Andrea
Laboratorio de Biología Celular y Retrovirus - CONICET, Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría "Dr. J. P. Garrahan", Ciudad Autónoma de Buenos Aires, Argentina.
International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
AIDS Res Hum Retroviruses. 2025 Jun;41(6):292-300. doi: 10.1089/aid.2024.0068. Epub 2025 Mar 19.
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.
人类嗜T淋巴细胞病毒1型（HTLV-1）是成人T细胞白血病/淋巴瘤（ATL/ATLL）的病原体，与HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）有关。影响该疾病发展的因素尚不清楚。大多数HTLV-1感染者终生无症状，而2.5%-5%会发展为ATLL，0.3%-2%会发展为HAM/TSP。全球约有1000万至2000万人感染HTLV-1。在阿根廷，HTLV-1感染尤其在与玻利维亚和巴拉圭接壤的东北部省份有记录。本研究旨在使用下一代测序分析来自无症状和有症状患者的9个HTLV-1完整基因组。进行了突变分析和病毒整合位点的鉴定。突变分析揭示了不同的突变模式，确定了与HAM/TSP患者和淋巴瘤患者相关的簇。发现了跨不同染色体的多个整合位点，表明随机整合且无特定热点。在一名淋巴瘤患者中鉴定出一个缺陷前病毒，可能影响免疫逃逸和克隆扩增。首次获得了阿根廷循环毒株的完整HTLV-1基因组序列。这有助于了解该病毒的遗传变异性及其在人类基因组中的整合位点，并揭示自然感染中HTLV-1前病毒的性质是复杂的。
