Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study

Abstract Objectives 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 d...

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Main Authors: Esmé Jansen van Vuren, Yolandi Breet, Adriaan Jacobs, Iolanthé M. Kruger, Monray Edward Williams
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Virology Journal
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Online Access:https://doi.org/10.1186/s12985-025-02891-8
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author Esmé Jansen van Vuren
Yolandi Breet
Adriaan Jacobs
Iolanthé M. Kruger
Monray Edward Williams
author_facet Esmé Jansen van Vuren
Yolandi Breet
Adriaan Jacobs
Iolanthé M. Kruger
Monray Edward Williams
author_sort Esmé Jansen van Vuren
collection DOAJ
description Abstract Objectives 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. Methods 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. Results 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. Conclusion 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.
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spelling doaj-art-426cf9ee13c24bc69bedde69666a9a082025-08-20T04:01:43ZengBMCVirology Journal1743-422X2025-08-0122111010.1186/s12985-025-02891-8Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory studyEsmé Jansen van Vuren0Yolandi Breet1Adriaan Jacobs2Iolanthé M. Kruger3Monray Edward Williams4Hypertension in Africa Research Team (HART), North-West UniversityHypertension in Africa Research Team (HART), North-West UniversityHypertension in Africa Research Team (HART), North-West UniversityAfrica Unit for Transdisciplinary Health Research (AUTHeR), North-West UniversityBiomedical and Molecular Metabolism Research (BioMMet), North-West UniversityAbstract Objectives 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12985-025-02891-8Cardiovascular diseaseCentral haemodynamicsArterial stiffnessHIVViral proteins
spellingShingle Esmé Jansen van Vuren
Yolandi Breet
Adriaan Jacobs
Iolanthé M. Kruger
Monray Edward Williams
Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study
Virology Journal
Cardiovascular disease
Central haemodynamics
Arterial stiffness
HIV
Viral proteins
title Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study
title_full Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study
title_fullStr Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study
title_full_unstemmed Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study
title_short Variation in HIV-1 Tat and Vpr protein amino acid sequences and its association with vascular health measures in a South African cohort: an exploratory study
title_sort variation in hiv 1 tat and vpr protein amino acid sequences and its association with vascular health measures in a south african cohort an exploratory study
topic Cardiovascular disease
Central haemodynamics
Arterial stiffness
HIV
Viral proteins
url https://doi.org/10.1186/s12985-025-02891-8
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