Human Metabolomics, North-West University, Potchefstroom, South Africa.
Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.
BMC Infect Dis. 2024 Sep 9;24(1):943. doi: 10.1186/s12879-024-09874-0.
HIV-1 has well-established mechanisms to disrupt essential pathways in people with HIV, such as inflammation and metabolism. Moreover, diversity of the amino acid sequences in fundamental HIV-1 proteins including Tat and Vif, have been linked to dysregulating these pathways, and subsequently influencing clinical outcomes in people with HIV. However, the relationship between Tat and Vif amino acid sequence variation and specific immune markers and metabolites of the tryptophan-kynurenine (Trp-Kyn) pathway remains unclear. Therefore, this study aimed to investigate the relationship between Tat/Vif amino acid sequence diversity and Trp-Kyn metabolites (quinolinic acid (QUIN), Trp, kynurenic acid (KA), Kyn and Trp/Kyn ratio), as well as specific immune markers (sCD163, suPAR, IL-6, NGAL and hsCRP) in n = 67 South African cART-naïve people with HIV.
Sanger sequencing was used to determine blood-derived Tat/Vif amino acid sequence diversity. To measure Trp-Kyn metabolites, a LC-MS/MS metabolomics platform was employed using a targeted approach. To measure immune markers, Enzyme-linked immunosorbent assays and the Particle-enhanced turbidimetric assay was used.
After adjusting for covariates, sCD163 (p = 0.042) and KA (p = 0.031) were higher in participants with Tat signatures N24 and R57, respectively, and amino acid variation at position 24 (adj R = 0.048, β = -0.416, p = 0.042) and 57 (adj R = 0.166, β = 0.535, p = 0.031) of Tat were associated with sCD163 and KA, respectively.
These preliminary findings suggest that amino acid variation in Tat may have an influence on underlying pathogenic HIV-1 mechanisms and therefore, this line of work merits further investigation.
HIV-1 已经建立了完善的机制来破坏 HIV 感染者体内的重要途径，如炎症和代谢途径。此外，Tat 和 Vif 等 HIV-1 基本蛋白的氨基酸序列多样性与这些途径的失调有关，进而影响 HIV 感染者的临床结局。然而，Tat 和 Vif 氨基酸序列变异与色氨酸-犬尿氨酸（Trp-Kyn）途径的特定免疫标志物和代谢物之间的关系尚不清楚。因此，本研究旨在探讨 Tat/Vif 氨基酸序列多样性与 Trp-Kyn 代谢物（喹啉酸（QUIN）、Trp、犬尿氨酸（KA）、Kyn 和 Trp/Kyn 比值）以及特定免疫标志物（sCD163、suPAR、IL-6、NGAL 和 hsCRP）之间的关系，共纳入 67 名南非未经 cART 治疗的 HIV 感染者。
采用 Sanger 测序法测定血液衍生的 Tat/Vif 氨基酸序列多样性。采用 LC-MS/MS 代谢组学平台采用靶向方法测定 Trp-Kyn 代谢物。采用酶联免疫吸附法和粒子增强比浊法测定免疫标志物。
在调整了协变量后，具有 Tat 特征 N24 和 R57 的参与者的 sCD163（p=0.042）和 KA（p=0.031）分别升高，Tat 第 24 位（调整后的 R=0.048，β=-0.416，p=0.042）和 57 位（调整后的 R=0.166，β=0.535，p=0.031）的氨基酸变异与 sCD163 和 KA 相关。
这些初步发现表明，Tat 的氨基酸变异可能对潜在的 HIV-1 致病机制有影响，因此值得进一步研究。
