Journal Article Epublish
PubMed: 39251983 DOI: 10.1186/s12879-024-09874-0
The association between HIV-1 Tat and Vif amino acid sequence variation, inflammation and Trp-Kyn metabolism: an exploratory investigation.
BMC Infect Dis 24(1):943
Authors: Monray E Williams, Levanco K Asia, Zander Lindeque, Esmé Jansen van Vuren
Affiliations
- Human Metabolomics, North-West University, Potchefstroom, South Africa.
- Human Metabolomics, North-West University, Potchefstroom, South Africa.
- 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.
Abstract
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
MeSH
Hiv-1, Amino Acids, Hiv, Genes, Vif, Genes, Tat, Amino Acid Sequence, Communicable Diseases