1. Natural Killer Cell Receptors and Ligands Are Associated With Markers of HIV-1 Persistence in Chronically Infected ART Suppressed Patients
- Author
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Geoffrey T. Ivison, Elena Vendrame, Giovanny J. Martínez-Colón, Thanmayi Ranganath, Rosemary Vergara, Nancy Q. Zhao, Maureen P. Martin, Sean C. Bendall, Mary Carrington, Joshua C. Cyktor, Deborah K. McMahon, Joseph Eron, R. Brad Jones, John W. Mellors, Ronald J. Bosch, Rajesh T. Gandhi, Susan Holmes, Catherine A. Blish, and The ACTG 5321 Team
- Subjects
Microbiology (medical) ,natural killer cells ,natural killer cell receptor ligands ,HIV cure ,Immunology ,HIV Infections ,Ligands ,Microbiology ,QR1-502 ,Virus Latency ,human immunodeficiency virus (HIV) ,Infectious Diseases ,HIV-1 ,Humans ,Receptors, Natural Killer Cell ,HIV latency - Abstract
The latent HIV-1 reservoir represents a major barrier to achieving a long-term antiretroviral therapy (ART)-free remission or cure for HIV-1. Natural Killer (NK) cells are innate immune cells that play a critical role in controlling viral infections and have been shown to be involved in preventing HIV-1 infection and, in those who are infected, delaying time to progression to AIDS. However, their role in limiting HIV-1 persistence on long term ART is still uncharacterized. To identify associations between markers of HIV-1 persistence and the NK cell receptor-ligand repertoire, we used twin mass cytometry panels to characterize the peripheral blood NK receptor-ligand repertoire in individuals with long-term antiretroviral suppression enrolled in the AIDS Clinical Trial Group A5321 study. At the time of testing, participants had been on ART for a median of 7 years, with virological suppression +CD56dimCD57-LILRB1-NKG2C-) was associated with lower HIV-1 cell associated DNA. Finally, we found that surface expression of HLA-Bw6 measured by CyTOF was associated with lower HIV-1 persistence. Genetic analysis revealed that this was driven by lower HIV-1 persistence in HLA-Bw4/6 heterozygotes. These findings suggest that there may be a role for NK cells in controlling HIV-1 persistence in individuals on long-term ART, which must be corroborated by future studies.
- Published
- 2022
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