Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response
- Vall d'Hebron Research Institute (VHIR), Spain
Abstract
HIV establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy, but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.
Data availability
The authors declare that the data supporting the findings of this study are available within the paper and its supplementary information files. Source data are provided with this paper.
Article and author information
Author details
Funding
Spanish National Plan for Scientific and Technical Research and Innovation (SAF2015-67334-R)
- Maria Buzon
Spanish National Plan for Scientific and Technical Research and Innovation (RTI2018-101082-B)
- Maria Buzon
Fundació La Marató TV3 (201805-10FMTV3)
- Maria Buzon
Fundació La Marató TV3 (201814-10FMTV3)
- Meritxell Genescà
Spanish Health Institute Carlos III (CP17/00179)
- Maria Buzon
Spanish National Plan for Scientific and Technical Research and Innovation (BES-2016-076382)
- Antonio Astorga-Gamaza
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Julie M Overbaugh, Fred Hutchinson Cancer Research Center, United States
Ethics
Human subjects: This study involves human samples. PBMCs from PLWH were obtained from the HIV unit of the Hospital Universitari Vall d'Hebron in Barcelona, Spain. Study protocols were approved by the corresponding Ethical Committees (Institutional Review Board numbers PR(AG)270/2015 and PR(AG)39/2016). PBMCs from healthy donors were obtained from the Blood and Tissue Bank, Barcelona, Spain. All subjects recruited to this study were adults who provided written informed consent. Samples were completely anonymous and untraceable and were prospectively collected and cryopreserved in the Biobank (register number C.0003590).
Version history
- Preprint posted: February 25, 2022 (view preprint)
- Received: March 1, 2022
- Accepted: May 23, 2022
- Accepted Manuscript published: May 26, 2022 (version 1)
- Version of Record published: June 8, 2022 (version 2)
Copyright
© 2022, Astorga-Gamaza 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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Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response
eLife 11:e78294.
https://doi.org/10.7554/eLife.78294
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