Human leukocyte antigen (HLA) diversity and clinical applications in South Africa

Mellet, Juanita; Tshabalala, Mqondisi; Agbedare, O.; Meyer, P.W.A.; Gray, Clive M.; Pepper, Michael Sean

doi:10.7196/samj.2019.v109i8b.13825

Cited by 12 publications

(14 citation statements)

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“…HLA class I allotypes play an important role in the control of HIV-1 viraemia [29]. Several HLA class I alleles that encode allotypes predicted to present epitopes identi ed in this study are known to be present in the South African population, including HLA-B*58:01 and HLA-A*02 that present SAAVKAACW (IN 123-131) and MASDFNLPPIV ( [22][23][24][25][26][27][28][29][30][31], respectively [28,30,49]. Past gene association studies showed that alleles within the HLA-B group correlate with greater viral control than alleles in the HLA-A and HLA-C groups [28][29]50].…”

Section: Discussionmentioning

confidence: 99%

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Nkone

Loubser

Quinn

et al. 2021

Preprint

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Background Despite multiple attempts, there is still no effective HIV-1 vaccine available. The HIV-1 polymerase (pol) gene is highly conserved and encodes cytotoxic T-lymphocyte (CTL) epitopes. In this study, deep sequencing was employed for characterisation of HIV-1 Pol CTL epitopes in mostly paired samples obtained during early and chronic stages of infection. Deep sequencing data was then compared to Sanger sequencing data only in samples obtained at baseline. Results Fifty-two participants were enrolled in the study. Their median age was 28 years (interquartile range: 24–32 years) and the majority of participants (92.3%) were female. Illumina minority variant analysis identified a significantly higher number of CTL epitopes (n = 65) compared to epitopes (n = 8) identified through Sanger sequencing. Most of the identified epitopes mapped to reverse transcriptase (RT) and integrase (IN) regardless of the method of sequencing. There was a significantly higher proportion of minority variant epitopes in RT (n = 39, 60.0%) compared to IN (n = 17, 26.2%) and PR (n = 9, 13.8%), p = 0.002 and < 0.0001, respectively. However, no significant difference was observed between the proportion of minority variant epitopes in IN versus PR, p = 0.06. Some epitopes were detected in either early or chronic HIV-1 infection whereas others were detected in both stages. Different distribution patterns of minority variant epitopes were observed in sample pairs; with some increasing or decreasing over time, while others remained constant. Some of the identified epitopes have not been previously reported for HIV-1 subtype C. There were also variants that could not be mapped to reported CTL epitopes in the Los Alamos HIV database. Conclusion Deep sequencing revealed many Pol CTL epitopes, including some not previously reported for HIV-1 subtype C. The findings of this study support the inclusion of RT and IN epitopes in HIV-1 vaccine candidates as these proteins harbour many CTL epitopes. Variants that were not mapped within CTL epitopes could represent new epitopes.

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Section: Discussionmentioning

confidence: 99%

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Nkone

Loubser

Quinn

et al. 2021

Preprint

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“…Alleles underlined are those that were reported to be protective [11,[28][29]49,50]. PR = protease; RT = reverse transcriptase; IN = integrase; HLA = human leukocyte antigen…”

Section: Pol Ctl Epitopes Based On Analysis Of Minority Variantsmentioning

confidence: 99%

Deep Sequencing of the HIV-1 Polymerase Gene for Characterisation of Cytotoxic T-Lymphocyte Epitopes During Early and Chronic Disease Stages

Nkone

Loubser

Quinn

et al. 2021

Preprint

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Background Despite multiple attempts, there is still no effective HIV-1 vaccine available. The HIV-1 polymerase (pol) gene is highly conserved and encodes cytotoxic T-lymphocyte (CTL) epitopes. The aim of the study was to characterise HIV-1 Pol CTL epitopes in mostly sample pairs obtained during early and chronic stages of infection. Methods Illumina deep sequencing was conducted for all samples while Sanger sequencing was only performed on baseline samples. Codons under immune selection pressure were assessed by computing nonsynonymous to synonymous mutation ratios using MEGA. Minority CTL epitope variants occurring at \(\ge\)5% were detected using low-frequency variant tool in CLC Genomics. Los Alamos HIV database was used for mapping mutations to known HIV-1 CTL epitopes. Results Fifty-two participants were enrolled in the study. Their median age was 28 years (interquartile range: 24–32 years) and majority of participants (92.3%) were female. Illumina minority variant analysis identified a significantly higher number of CTL epitopes (n = 65) compared to epitopes (n = 8) identified through Sanger sequencing. Most of the identified epitopes mapped to reverse transcriptase (RT) and integrase (IN) regardless of sequencing method. There was a significantly higher proportion of minority variant epitopes in RT (n = 39, 60.0%) compared to IN (n = 17, 26.2%) and PR (n = 9, 13.8%), p = 0.002 and < 0.0001, respectively. However, no significant difference was observed between the proportion of minority variant epitopes in IN versus PR, p = 0.06. Some epitopes were detected in either early or chronic HIV-1 infection whereas others were detected in both stages. Different distribution patterns of minority variant epitopes were observed in sample pairs; with some increasing or decreasing over time, while others remained constant. Some of the identified epitopes have not been previously reported for HIV-1 subtype C. There were also variants that could not be mapped to reported CTL epitopes in the Los Alamos HIV database. Conclusion Deep sequencing revealed many Pol CTL epitopes, including some not previously reported for HIV-1 subtype C. The findings of this study support the inclusion of RT and IN epitopes in HIV-1 vaccine candidates as these proteins harbour many CTL epitopes.

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“…This diversity presents a crucial consideration that influences the outcome of solid organ and hematopoietic stem cell transplant 2 . The recent adoption of next‐generation sequencing‐based HLA typing methodologies for the identification of compatible organ donor‐recipient pairs has aided the identification of novel HLA allelic variants 3,4 . This is especially true in African populations where the HLA allelic diversity remains relatively undefined when compared to European and North American populations 3,4 …”

Section: Figurementioning

confidence: 99%

“…2 The recent adoption of next-generation sequencing-based HLA typing methodologies for the identification of compatible organ donor-recipient pairs has aided the identification of novel HLA allelic variants. 3,4 This is especially true in African populations where the HLA allelic diversity remains relatively undefined when compared to European and North American populations. 3,4 Here we describe the detection of a novel HLA-DQB1 allele in a South African cardiac transplant candidate.…”

mentioning

confidence: 99%

“…3,4 This is especially true in African populations where the HLA allelic diversity remains relatively undefined when compared to European and North American populations. 3,4 Here we describe the detection of a novel HLA-DQB1 allele in a South African cardiac transplant candidate. The novel allele was detected during HLA typing of the transplant candidate by next-generation sequencing on the Illumina MiSeq platform using a DNA library prepared using commercially available reagents (GenDX, Utrecht, Netherlands).…”

mentioning

confidence: 99%

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Characterization of the novel HLA‐DQB105:272* allele in a South African patient by next‐generation sequencing

Valley‐Omar

Maart

Seele

et al. 2020

HLA

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Human leukocyte antigen (HLA) diversity and clinical applications in South Africa

Abstract: This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Cited by 12 publications

References 50 publications

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Deep Sequencing of the HIV-1 Polymerase Gene for Characterisation of Cytotoxic T-Lymphocyte Epitopes During Early and Chronic Disease Stages

Characterization of the novel HLA‐DQB105:272* allele in a South African patient by next‐generation sequencing

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Human leukocyte antigen (HLA) diversity and clinical applications in South Africa

Abstract: This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Cited by 12 publications

References 50 publications

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

Deep Sequencing of the HIV-1 Polymerase Gene for Characterisation of Cytotoxic T-Lymphocyte Epitopes During Early and Chronic Disease Stages

Characterization of the novel HLA‐DQB1*05:272 allele in a South African patient by next‐generation sequencing

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Characterization of the novel HLA‐DQB105:272* allele in a South African patient by next‐generation sequencing