Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8
            <sup>+</sup>
            T Cells

Payne, Rebecca; Kløverpris, Henrik N.; Sacha, Jonah B.; Brumme, Zabrina L.; Brumme, Chanson J.; Buus, Søren; Sims, Stuart; Hickling, Stephen; Riddell, Lynn; Chen, Fabian; Luzzi, Graz; Edwards, Anne; Phillips, Rodney E.; Prado, Julia G.; Goulder, Philip

doi:10.1128/jvi.00793-10

Cited by 82 publications

(101 citation statements)

References 40 publications

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“…That the majority of HLA-associated polymorphisms occur outside known epitopes suggests that many epitopes remain undiscovered; indeed, HLA-associated polymorphisms represent an excellent tool to guide epitope discovery as they are unbiased by consensus sequences or limited knowledge of binding motifs (5,13,17,92). This study also extends our understanding of the proportion of population-level HIV-1 diversity attributable to HLA selection pressures, identifies abrogation of HLA-peptide binding as a predominant escape mechanism, suggests a potential evolutionary mechanism underlying differential escape between allele group members, and provides an extensive reference of proteome-wide HLA-mediated escape pathways.…”

Section: Discussionmentioning

confidence: 99%

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Carlson

Brumme

Martin

et al. 2012

J Virol

266

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i HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies. HIV-1 is notorious for its genetic diversity and its ability to adapt to selection pressures (44,87,116). Despite this, within-host HIV-1 evolution in response to antiretroviral (61, 72), host cellular immune (15,50,71,94,95), antibody (46), and vaccine-induced (103) selection pressures occurs along generally predictable mutational pathways (3, 84). Studying these evolutionary pathways can offer insight into the immunopathogenesis of HIV-1 and may help inform the design of immune-based interventions and vaccines.Substantial progress has been made in our understanding of HIV-1's ability to evade human leukocyte antigen (HLA) class I-restricted CD8 ϩ cytotoxic T-lymphocytes (CTL). In particular, application of novel statistical methods (13,25,84) to large population-based data sets of linked host and viral genetic information has facilitated the systematic identification of HLA-associated immune escape and covarying mutations in 20,60,81,99,104), revealing important insights into HIV-1 adaptation to its host. We now appreciate that immune selection represents a major force shaping HIV-1 diversity (3,80,...

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Section: Discussionmentioning

confidence: 99%

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Carlson

Brumme

Martin

et al. 2012

J Virol

266

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“…The first relates to immunoevasion mediated by HIV Nef, which acts to downregulate MHC-I on infected cells, thereby diminishing recognition by CD8 + T cells (61). In productive HIV replication, Nef immunoevasion is likely limited -to some extent -by the early presentation of antigen from incoming virions prior to Nef-mediated MHC-I downregulation (within 2-6 hours of infection) (62)(63)(64)(65)(66)(67)(68)(69)(70). In the setting of reactivation from latency there is no parallel to this eclipse phase, and the expression of late gene products (such as Gag) will occur only after MHC-I downregulation occurs.…”

Section: Discussionmentioning

confidence: 99%

Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells

Huang

Ren

Thomas

et al. 2018

Journal of Clinical Investigation

155

151

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“…In ARV-suppressed patients, the lack of viral replication negates the issue of ongoing viral escape, though sequence diversity in the existing reservoir is an important consideration. In unsuppressed patients, it is critical for CD8 + T cells to be able to recognize infected cells quickly, before virus can be produced (82)(83)(84)(85). In ARV-treated subjects, rapid killing may not be important, provided that transmission of infection to other cells is suppressed by ARVs.…”

Section: Ctl-mediated Approaches For Eradication Of Hiv Infectionmentioning

confidence: 99%

HIV-specific CD8+ T cells and HIV eradication

Jones¹,

Walker²

2016

Journal of Clinical Investigation

111

106

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Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8 ⁺ T Cells

Cited by 82 publications

References 40 publications

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells

HIV-specific CD8+ T cells and HIV eradication

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Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8 + T Cells

Cited by 82 publications

References 40 publications

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells

HIV-specific CD8+ T cells and HIV eradication

Contact Info

Product

Resources

About

Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8 ⁺ T Cells