Jansen van Vuren Esmé, Breet Yolandi, Jacobs Adriaan, Kruger Iolanthé M, Williams Monray Edward
Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.
South African Medical Research Council: Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.
Virol J. 2025 Aug 4;22(1):266. doi: 10.1186/s12985-025-02891-8.
Human immunodeficiency virus (HIV)-1 is associated with adverse cardiovascular-related outcomes. Subtype-specific variations in the amino acid sequences of Tat and Vpr HIV-1 proteins are associated with differential clinical outcomes in people living with HIV (PLHIV). Given the diverse clinical outcomes related to different HIV subtypes, it is crucial to evaluate the variations in the sequence of Tat and Vpr amino acids in geographical regions where subtype C predominates, such as South Africa. This study aimed to determine whether specific Tat and Vpr protein amino acid variants (alone or in combination) are associated with vascular health measures and predict incident hypertension and all-cause mortality over a five-year period.
A cohort of n = 60 treatment-naïve PLHIV at baseline and n = 35 at a five-year follow-up was investigated. Standardized vascular health measures, including carotid intima-media thickness (cIMT), cross-sectional wall area (CSWA) and carotid-radial pulse wave velocity (crPWV), as well as Sanger sequencing for Tat/Vpr analysis, were performed. The associations of vascular health measures with Tat and Vpr amino acid variants were investigated.
We found that the variation in amino acid sequence in Tat only (p = 0.039) and Tat/Vpr (p < 0.001) were associated with crPWV at baseline. Variation in the Tat and Vpr amino acid sequence did not predict incident hypertension in five years or all-cause mortality.
The variants of the Tat and Vpr amino acid sequence were associated with arterial stiffness, which may be an underlying mechanism for cardiovascular disease development in PLHIV.
人类免疫缺陷病毒1型（HIV-1）与不良心血管相关结局有关。Tat和Vpr HIV-1蛋白氨基酸序列的亚型特异性变异与HIV感染者（PLHIV）的不同临床结局相关。鉴于与不同HIV亚型相关的临床结局多样，评估在C亚型占主导的地理区域（如南非）中Tat和Vpr氨基酸序列的变异至关重要。本研究旨在确定特定的Tat和Vpr蛋白氨基酸变体（单独或组合）是否与血管健康指标相关，并预测五年内高血压的发生和全因死亡率。
对一组基线时n = 60例未经治疗的PLHIV和五年随访时n = 35例进行了调查。进行了标准化的血管健康指标检测，包括颈动脉内膜中层厚度（cIMT）、横截面积（CSWA）和颈-桡脉搏波速度（crPWV），以及用于Tat/Vpr分析的桑格测序。研究了血管健康指标与Tat和Vpr氨基酸变体之间的关联。
我们发现仅Tat（p = 0.039）和Tat/Vpr（p < 0.001）的氨基酸序列变异与基线时的crPWV相关。Tat和Vpr氨基酸序列的变异在五年内未预测高血压的发生或全因死亡率。
Tat和Vpr氨基酸序列变体与动脉僵硬度相关，这可能是PLHIV心血管疾病发展的潜在机制。
