Observational studyPLoS medicine2015
Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa.
Observational study in PLoS medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 81 citations in OpenAlex.
- NK cell immunotherapy after analytic treatment interruption is associated with HIV viral control.Molecular therapy. Advances · 2026Article
- Multiplex engineering of rhesus macaque NK cells enhances homing to sites of HIV replication in B cell follicles.bioRxiv : the preprint server for biology · 2026Article
- NK cell immunotherapy administered at the time of HIV recrudescence is associated with viral control.bioRxiv : the preprint server for biology · 2025Article
- Harnessing innate immunity: natural killer cells and innate immune responses in reservoir clearance.Current opinion in HIV and AIDS · 2025Review
- A transatlantic joint lab model for interdisciplinary research.Nature microbiology · 2025Article
- HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production.iScience · 2025Article
- Peptide-specific natural killer cell receptors.Oxford open immunology · 2025Review
- Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness.PLoS pathogens · 2024Article
- HLA-C Peptide Repertoires as Predictors of Clinical Response during Early SARS-CoV-2 Infection.Life (Basel, Switzerland) · 2024Article
- Unveiling the Significance of HLA and KIR Diversity in Underrepresented Populations.Biomedicines · 2024Review
- In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.Oncoimmunology · 2024Review
- Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection.Microorganisms · 2023Review
- A mutagenesis study of autoantigen optimization for potential T1D vaccine design.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Risk Factors for Ebola Virus Persistence in Semen of Survivors in Liberia.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?Frontiers in immunology · 2023Review
- A humanized mouse model to study NK cell biology during HIV infection.The Journal of clinical investigation · 2022Article
- Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells.EMBO reports · 2022Article
- HIV-1 Nef-mediated downregulation of CD155 results in viral restriction by KIR2DL5+ NK cells.PLoS pathogens · 2022Article
- Natural killer cells in antiviral immunity.Nature reviews. Immunology · 2022Review
- Latency reversal plus natural killer cells diminish HIV reservoir in vivo.Nature communications · 2022Article
Corrections and comments
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Authors and funding
22 authors at 12 institutions in 5 countries.
Funding
Abstract
backgroundViruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure. METHODS AND
findingsTwo sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I-presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control.
conclusionsThese data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.