Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

Lazaryan, Aleksandr; Song, Wei; Lobashevsky, Elena; Tang, Jianming; Shrestha, Sadeep; Zhang, Kui; Gardner, Lytt I.; McNicholl, Janet M.; Wilson, Craig M.; Klein, Robert S.; Rompalo, Anne; Mayer, Kenneth H.; Sobel, Jack D.; Kaslow, Richard A.

doi:10.1128/jvi.01962-09

Cited by 32 publications

(32 citation statements)

References 45 publications

(59 reference statements)

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“…In other words, similarity or difference in peptide-binding preferences alone may not fully capture the spectrum of concerted and evolving immune function that is essential to durable containment of HIV-1 infection (44). Either way, ongoing efforts to expand the sub-Saharan African cohorts of seroconverters should allow detailed analysis of HLA sequence motifs and other related properties (e.g., supertypes and frequencies) (47,48).…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen Variants B44 and B57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Tang

Cormier

Gilmour

et al. 2011

J Virol

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As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan African countries, we have identified 134 seroconverters (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point) viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57 had much lower peak viral loads (VLs) than SCs without these variants (adjusted linear regression beta values of ؊1.08 ؎ 0.26 log 10 [mean ؎ standard error] and ؊0.83 ؎ 0.27 log 10 , respectively; P < 0.005 for both), after accounting for several nongenetic factors, including gender, age at estimated date of infection, duration of infection, and country of origin. These findings were confirmed by alternative models in which major viral subtypes (A1, C, and others) in the same SCs replaced country of origin as a covariate (P < 0.03). Both B*44 and B*57 were also highly favorable (P < 0.03) in analyses of set-point VLs. Moreover, B*44 was associated with relatively high CD4 ؉ T-cell counts during early chronic infection (P ‫؍‬ 0.02). Thus, at least two common HLA-B variants showed strong influences on acute-phase as well as early chronic-phase VL, regardless of the infecting viral subtype. If confirmed, the identification of B*44 as another favorable marker in primary HIV-1 infection should help dissect mechanisms of early immune protection against HIV-1 infection.HIV-1 viral load (VL or viremia), in the typical form of viral RNA concentration in plasma, has both epidemiological and clinical implications because of its dual impact on transmission (18,30,71) and on the rate of disease progression (58, 59). In most studies, a quantitative measure of VL is used without reference to estimated date of infection (EDI), under the assumption that patients are seldom observed during acute-phase (peak) infection and that the early chronic-phase (set-point) VL is usually stable for years in patients with no apparent manifestations of immunodeficiency. Factors known or suspected to influence VL range from viral mutations (changes in replication fitness or switches in coreceptor tropism) (15,28,39,72) to host genes that govern innate and adaptive immune responses (54,75,81,83,84,86).Within the human nuclear genome, human leukocyte antigen (HLA) class I genes are the most convincing (and universally applicable) quantitative trait loci for HIV-1 viremia (14,16,17,66). However, the individual HLA alleles, haplotypes, and supertypes with reported impacts on HIV-1 VL are not always clear because their distribution and patterns of linkage disequilibrium often differ from one population to another (7,53,63). Consensus findings have been limited to a few variants like B*27 and B*57 (9, 80), although more recent work based on African cohorts has yielded consensus results for additional variants, including A*74, B*13, and B*81, that are often favorable (49, 81). The HLA class I heavy chains encoded by these alleles differentially present highly conserved viral epitopes for cytotoxic T-lymphocyte (CTL) responses (5,29,39). Su...

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Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen Variants B44 and B57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Tang

Cormier

Gilmour

et al. 2011

J Virol

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“…Accordingly, recent epidemiological studies have yielded ambiguous results concerning the association of HLA supertypes with immune responses. One group studying the cytokine profile of children after vaccination against rubella virus [67] has found correlations between the intensity of some types of cytokine releases and some HLA supertypes (A1, A2, and A3), while correlations between some supertypes and HIV control have also been reported [68]. However, another study analyzing the selection pressures imposed by HLA class I molecules on human immunodeficiency virus (HIV) epitopes [69] has found no uniform effects of supertypes but rather substantially different evasive mutations favored by the presence of each allele.…”

Section: Mhc Class I Processing: What Do the Ligands Tell Us?mentioning

confidence: 99%

Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands

Mester

Hoffmann

Stevanović

2011

Cell. Mol. Life Sci.

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Short peptides derived from intracellular proteins and presented on MHC class I molecules on the cell surface serve as a showcase for the immune system to detect pathogenic or malignant alterations inside the cell, and the sequencing and analysis of the presented peptide pool has received considerable attention over the last two decades. In this review, we give a comprehensive presentation of the methods employed for the large-scale qualitative and quantitative analysis of the MHC class I ligandome. Furthermore, we focus on insights gained into the underlying processing pathway, especially involving the roles of the proteasome, the TAP complex, and the peptide specificities and motifs of MHC molecules. The identification of post-translational modifications in MHC ligands and their implications for processing are also considered. Finally, we review the correlations of the ligandome to the proteome and the transcriptome.

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“…1,9,10 The clearest genotypic data have been established for HLA-B*5701, HLA-B*5703, HLA-B*2705, 5,[11][12][13] and, in African ethnicities, HLA-B*5801. 14,15 Further studies suggest a beneficial impact of HLA-B*14, HLA-B*51, HLA-B*81, and HLA-Cw*1402. Viral escape mutations in CD8 T-cell epitopes that coincide with viremia increase demonstrate the relevance of these responses in vivo.…”

Section: Introductionmentioning

confidence: 99%

High-dimensional immunomonitoring models of HIV-1–specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control

Ndhlovu

Chibnik

Proudfoot

et al. 2013

Blood

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Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

Cited by 32 publications

References 45 publications

Human Leukocyte Antigen Variants B44 and B57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Human Leukocyte Antigen Variants B44 and B57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands

High-dimensional immunomonitoring models of HIV-1–specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control

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Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

Cited by 32 publications

References 45 publications

Human Leukocyte Antigen Variants B*44 and B*57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Human Leukocyte Antigen Variants B*44 and B*57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands

High-dimensional immunomonitoring models of HIV-1–specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control

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Resources

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Human Leukocyte Antigen Variants B44 and B57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

Human Leukocyte Antigen Variants B44 and B57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes