Arnaut Nicoleta, Slevin Mark, Bănescu Claudia, Straistă Mihaela, Caruso Arnaldo, Caccuri Francesca
Centre for Advanced Medical and Pharmaceutical Research, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania.
Genetics Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania.
Viruses. 2025 Mar 24;17(4):463. doi: 10.3390/v17040463.
Non-Hodgkin lymphoma (NHL) remains the most common malignancy and cause of death among human immunodeficiency virus (HIV-1)-positive individuals, its prevalence remaining even after the introduction of combined antiretroviral therapy (cART). The mechanisms underlying B-cell tumorigenesis are still poorly understood; however, recently, a key role for p17 variants (vp17s) in lymphoma development has been clearly elucidated. Here, we describe findings on lymphomagenic vp17s and discuss their potential role as diagnostic and prognostic markers that could be used to predict the HIV-positive patients at higher risk of developing lymphoma. Specifically, vp17s endowed with amino acid (aa) insertions in their C-terminal region, at positions 114-115 (Glu-Lys), 117-118 (Ala-Ala) and 125-126 (Gly-Asp), were found to be significantly more prevalent in HIV-positive individuals with lymphoma as compared to those without. Alterations in the primary aa sequences destabilize the protein, exposing a previously hidden functional epitope which interacts with protease-activated receptor-1 (PAR-1) and stimulates the protein kinase B pathway, conferring oncogenic potential to vp17s and possibly contributing to lymphomagenesis. Therefore, ultradeep sequencing technologies, such as next-generation sequencing, could serve as a valuable screening tool for identifying and monitoring the HIV-positive patients at higher risk of developing lymphoma, paving the way for targeted preventive intervention strategies.
非霍奇金淋巴瘤（NHL）仍然是人类免疫缺陷病毒（HIV-1）阳性个体中最常见的恶性肿瘤和死亡原因，即使在引入联合抗逆转录病毒疗法（cART）后其患病率依然居高不下。B细胞肿瘤发生的潜在机制仍知之甚少；然而，最近，p17变体（vp17s）在淋巴瘤发展中的关键作用已得到明确阐明。在此，我们描述了淋巴瘤发生相关vp17s的研究结果，并讨论了它们作为诊断和预后标志物的潜在作用，这些标志物可用于预测有更高淋巴瘤发生风险的HIV阳性患者。具体而言，在其C末端区域第114 - 115位（Glu-Lys）、117 - 118位（Ala-Ala）和125 - 126位（Gly-Asp）有氨基酸（aa）插入的vp17s，在患有淋巴瘤的HIV阳性个体中比未患淋巴瘤的个体更为显著地普遍存在。一级氨基酸序列的改变使蛋白质不稳定，暴露出一个先前隐藏的功能性表位，该表位与蛋白酶激活受体-1（PAR-1）相互作用并刺激蛋白激酶B途径，赋予vp17s致癌潜力，并可能促成淋巴瘤的发生。因此，诸如新一代测序等超深度测序技术可作为一种有价值的筛查工具，用于识别和监测有更高淋巴瘤发生风险的HIV阳性患者，为有针对性的预防干预策略铺平道路。
