Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population

(1) Background: Human Leukocyte Antigen (HLA) genetics substantially affect viral infection outcomes. SARS-CoV-2 continues to evolve, potentially escaping HLA presentation and hindering immune control. However, studies on HLA alleles in diverse non-Western populations remain limited. Therefore, we a...

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Main Authors: Amal Haraka, Sanjay Mehta, Tala Al-Rousan
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:COVID
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Online Access:https://www.mdpi.com/2673-8112/5/4/53
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author Amal Haraka
Sanjay Mehta
Tala Al-Rousan
author_facet Amal Haraka
Sanjay Mehta
Tala Al-Rousan
author_sort Amal Haraka
collection DOAJ
description (1) Background: Human Leukocyte Antigen (HLA) genetics substantially affect viral infection outcomes. SARS-CoV-2 continues to evolve, potentially escaping HLA presentation and hindering immune control. However, studies on HLA alleles in diverse non-Western populations remain limited. Therefore, we aimed to investigate whether mutations in successive SARS-CoV-2 variants have led to viral escape from common HLA class I alleles in the Saudi Arabian population. (2) Methods: The binding affinities of spike protein epitopes for common Saudi HLA alleles (HLA-A02:01, HLA-C06:02, and HLA-B51:01) were predicted across major SARS-CoV-2 strains using NetMHCpan. One-way ANOVA, one-sample <i>t</i>-tests, and pairwise chi-square analyses were performed to assess the differences in binding affinities and epitope binding categories among strains. (3) Results: One-way ANOVA revealed significant differences in binding affinities among SARS-CoV-2 strains for HLA-A02:01 and HLA-C06:02, but not for HLA-B51:01. One-sample <i>t</i>-tests revealed significant differences in mean binding affinity scores compared to a theoretical mean of 0 for all strain–HLA allele combinations, except for HLA-B51:01. Pairwise chi-square analyses identified significant differences in the epitope binding category distribution between Alpha and Epsilon strains, as well as between Epsilon and Gamma strains for HLA-B51:01. (4) Conclusions: The evolution of SARS-CoV-2 has enabled its escape from common HLA alleles in Saudis. Tracking population-specific HLA binding profiles is crucial for the elucidation of associated evasion mechanisms and guiding the design of future vaccines against COVID-19.
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spelling doaj-art-ae51d452b7b84334a76c6f06d0581f772025-08-20T02:17:19ZengMDPI AGCOVID2673-81122025-04-01545310.3390/covid5040053Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian PopulationAmal Haraka0Sanjay Mehta1Tala Al-Rousan2Clinical Research, University of California San Diego, San Diego, CA 92093, USADivision of Infectious Diseases & Global Public Health, University of California San Diego, La Jolla, CA 92093, USAHerbert Wertheim School of Public Health, University of California San Diego, San Diego, CA 92093, USA(1) Background: Human Leukocyte Antigen (HLA) genetics substantially affect viral infection outcomes. SARS-CoV-2 continues to evolve, potentially escaping HLA presentation and hindering immune control. However, studies on HLA alleles in diverse non-Western populations remain limited. Therefore, we aimed to investigate whether mutations in successive SARS-CoV-2 variants have led to viral escape from common HLA class I alleles in the Saudi Arabian population. (2) Methods: The binding affinities of spike protein epitopes for common Saudi HLA alleles (HLA-A02:01, HLA-C06:02, and HLA-B51:01) were predicted across major SARS-CoV-2 strains using NetMHCpan. One-way ANOVA, one-sample <i>t</i>-tests, and pairwise chi-square analyses were performed to assess the differences in binding affinities and epitope binding categories among strains. (3) Results: One-way ANOVA revealed significant differences in binding affinities among SARS-CoV-2 strains for HLA-A02:01 and HLA-C06:02, but not for HLA-B51:01. One-sample <i>t</i>-tests revealed significant differences in mean binding affinity scores compared to a theoretical mean of 0 for all strain–HLA allele combinations, except for HLA-B51:01. Pairwise chi-square analyses identified significant differences in the epitope binding category distribution between Alpha and Epsilon strains, as well as between Epsilon and Gamma strains for HLA-B51:01. (4) Conclusions: The evolution of SARS-CoV-2 has enabled its escape from common HLA alleles in Saudis. Tracking population-specific HLA binding profiles is crucial for the elucidation of associated evasion mechanisms and guiding the design of future vaccines against COVID-19.https://www.mdpi.com/2673-8112/5/4/53HLA class I allelesSARS-CoV-2 variantsSaudi Arabian populationviral escape mutationsepitope binding affinityNetMHCpan
spellingShingle Amal Haraka
Sanjay Mehta
Tala Al-Rousan
Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population
COVID
HLA class I alleles
SARS-CoV-2 variants
Saudi Arabian population
viral escape mutations
epitope binding affinity
NetMHCpan
title Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population
title_full Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population
title_fullStr Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population
title_full_unstemmed Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population
title_short Impacts of HLA Genetics on the SARS-CoV-2 Spike Proteins in the Arabian Population
title_sort impacts of hla genetics on the sars cov 2 spike proteins in the arabian population
topic HLA class I alleles
SARS-CoV-2 variants
Saudi Arabian population
viral escape mutations
epitope binding affinity
NetMHCpan
url https://www.mdpi.com/2673-8112/5/4/53
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