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Published (Version of Record)CC BY-NC V4.0, Open Access
Journal article
HIV-1 adapts to HLA class II-associated selection pressure exerted by CD4 + and CD8 + T cells
Science advances, Vol.11(7), eadr4238
2025
PMCID: PMC11827868
PMID: 39951541
Abstract
Developing an effective HIV-1 vaccine is a global health priority, but HIV-1 mutational escape from T cells poses a challenge. While escape from human leukocyte antigen class I (HLA-I)–restricted CD8+ T cells is well characterized, less is known about HLA-II–restricted T cell escape. We used computational methods to identify 149 sites across the HIV-1 clade B genome under HLA-II–associated selection. Functional assays, including activation-induced intracellular cytokine staining and enzyme-linked immunospot for interferon-γ, revealed diverse mechanisms of HIV-1 adaptation to HLA-II–associated immune pressure, ranging from loss to sustained antigen recognition. T cell receptor and RNA sequencing demonstrated variable clonotype overlap of T cell clones to recognize adapted versus non-adapted peptides, with cells targeting adapted peptides exhibiting a dysfunctional transcriptomic state. Moreover, incorporating HLA-II–associated adaptation strengthened the correlation between Gag-specific viral adaptation and poor disease outcomes. Last, we mapped viral regions prone to HLA-II–associated adaptation and found that these adaptations can increase in frequency within populations.
Details
- Title
- HIV-1 adapts to HLA class II-associated selection pressure exerted by CD4 + and CD8 + T cells
- Authors/Creators
- Eric Alves - The University of Western AustraliaJennifer Currenti - The University of Western AustraliaKeeley Crawford - The University of Western AustraliaAbha Chopra - Murdoch UniversityRamesh Ram - Murdoch UniversityLouise Barnett - Vanderbilt University Medical CenterJames F Read - University of ArizonaMarwah Al-Kaabi - The University of Western AustraliaIan James - Murdoch UniversityJonathan M Carlson - MicrosoftMax Eton - The University of Western AustraliaSophie Stelmach - The University of Western AustraliaPooja Deshpande - The University of Western AustraliaMark A Pilkinton - Vanderbilt University Medical CenterWyatt J McDonnell - Vanderbilt University Medical CenterAnthony Bosco - University of ArizonaSimon A Mallal - Murdoch UniversityMina John - Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia, AustraliaSpyros A Kalams - Vanderbilt University Medical CenterSilvana Gaudieri - Murdoch University
- Publication Details
- Science advances, Vol.11(7), eadr4238
- Publisher
- American Association for the Advancement of Science (AAAS)
- Number of pages
- 17
- Grant note
- National Health and Medical Research Council grant: APP1148284 Sir Charles Gairdner Hospital FoundationPathWestUWA Research Collaboration AwardNational Institutes of Health-funded Tennessee Center for AIDS Research grant: P30 AI110527 Australian Government Research Training Program ScholarshipBioZone Completion ScholarshipFulbright Future Scholarship (funded by The Kinghorn Foundation)
This work was supported by a National Health and Medical Research Council grant (APP1148284) awarded to S.G., a grant from the Sir Charles Gairdner Hospital Foundation and PathWest awarded to S.G., a UWA Research Collaboration Award awarded to S.G. and A.B., and a National Institutes of Health-funded Tennessee Center for AIDS Research grant (P30 AI110527) awarded to S.A.K. and S.A.M. E.A. is a recipient of an Australian Government Research Training Program Scholarship, BioZone Completion Scholarship, and Fulbright Future Scholarship (funded by The Kinghorn Foundation). M.A. is a recipient of an Australian Government Research Training Program Scholarship. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Identifiers
- 991005742485807891
- Copyright
- © 2025 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases; Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology