Journal article
HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses
PLoS pathogens, Vol.11(8), pp.e1005111-e1005111
08/01/2015
DOI: 10.1371/journal.ppat.1005111
PMCID: PMC4547780
PMID: 26302050
Abstract
Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution.
Details
- Title: Subtitle
- HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses
- Creators
- Nathan Erdmann - University of Alabama at BirminghamVictor Y Du - University of Alabama at BirminghamJonathan Carlson - MicrosoftMalinda Schaefer - Emory UniversityAlexander Jureka - University of Alabama at BirminghamSarah Sterrett - University of Alabama at BirminghamLing Yue - Emory UniversityDario Dilernia - Emory UniversityShabir Lakhi - Emory and Henry CollegeJianming Tang - University of Alabama at BirminghamJohn Sidney - La Jolla Institute For Allergy & ImmunologyJill Gilmour - International HIV/AIDS AllianceSusan Allen - Emory UniversityEric Hunter - Emory UniversitySonya Heath - University of Alabama at BirminghamAnju Bansal - University of Alabama at BirminghamPaul A Goepfert - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.11(8), pp.e1005111-e1005111
- DOI
- 10.1371/journal.ppat.1005111
- PMID
- 26302050
- PMCID
- PMC4547780
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Grant note
- R01 AI084772 / NIAID NIH HHS R01 AI064060 / NIAID NIH HHS 5R01AI064060-10 / NIAID NIH HHS 5R01AI084772-05 / NIAID NIH HHS 1R01AI112566-01A1 / NIAID NIH HHS R01 AI112566 / NIAID NIH HHS
- Language
- English
- Date published
- 08/01/2015
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984696761902771
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