The HIV-1 latent reservoir is largely sensitive to circulating T cells
- University of North Carolina at Chapel Hill, United States
- British Columbia Centre for Excellence in HIV/AIDS, Canada
- University of California, San Francisco, United States
Abstract
HIV-1 specific CD8+ T cells are an important component of HIV-1 curative strategies. Viral variants in the HIV-1 reservoir may limit the capacity of T cells to detect and clear virus-infected cells. We investigated the patterns of T cell escape variants in the replication-competent reservoir of 25 persons living with HIV-1 (PLWH) durably suppressed on ART. We identified all reactive T cell epitopes in the HIV-1 proteome for each participant and sequenced HIV-1 outgrowth viruses from resting CD4+ T cells. All non-synonymous mutations in reactive T cell epitopes were tested for their effect on the size of the T cell response, with a ≥50% loss defined as an escape mutation. The majority (68%) of T cell epitopes harbored no detectable escape mutations. These findings suggest that circulating T cells in PLWH on ART could contribute to control of rebound and could be targeted for boosting in curative strategies.
Data availability
Sequencing data have been deposited in Gen Bank under PRJNA666896, MT307344-MT308415 and MW054719-MW054856All data generated (raw) or analyzed during this study are included in the manuscript and supporting files (supplemental files).
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Primer ID sequencing for QVOA HIV sequenceNCBI Bioproject, PRJNA666896.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (P30 AI50410)
- Ronald Swanstrom
National Institute of Allergy and Infectious Diseases (U01 AI103390)
- Adaora A Adimora
National Institute of Allergy and Infectious Diseases (U01 AI034989)
- Nadia Roan
National Institute of Allergy and Infectious Diseases (U01 AI131310)
- Joanna A Warren
- Shuntai Zhou
- Yinyan Xu
- Nilu Goonetilleke
National Institute of Allergy and Infectious Diseases (R01 AI140970)
- Ronald Swanstrom
National Institute of Allergy and Infectious Diseases (UM1AI126617)
- Daniel R MacMillan
- Zabrina L Brumme
National Institute of Allergy and Infectious Diseases (1UM1AI126619)
- Joanna A Warren
- Shuntai Zhou
- Julia M Sung
- JoAnn D Kuruc
- Cynthia L Gay
- David M Margolis
- Nancie Archin
- Nilu Goonetilleke
Canadian Institutes of Health Research (PJT-148612)
- Daniel R MacMillan
- Zabrina L Brumme
Canadian Institutes of Health Research (PJT-159625)
- Daniel R MacMillan
- Zabrina L Brumme
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Participants were enrolled with the following IRB approved studies: 1) CID 0819 - Apheresis Procedures to Obtain Leukocytes for Research Studies from HIV Positive Participants (08-1575), 2) The UNC Women's Interagency HIV Study (WIHS) (12-1660). Review and implementation of all protocols utilized for the collection of samples for this this analysis were approved by the University of North Carolina at Chapel Hill Biomedical Institutional Review Board (IRB) and the University of California at San Francisco IRB. All participants provided written informed consent. All experimental protocols were approved by local Institutional Biomedical Review Boards (ethics numbers: 14-0741, 11-0228, and 13-3613, 15-1626) and performed in accordance with the relevant guidelines.
Copyright
© 2020, Warren et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The HIV-1 latent reservoir is largely sensitive to circulating T cells
eLife 9:e57246.
https://doi.org/10.7554/eLife.57246
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