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.
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.
- Maria Buzon
- Maria Buzon
- Maria Buzon
- Meritxell Genescà
- Maria Buzon
- Antonio Astorga-Gamaza
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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).
- Julie M Overbaugh, Fred Hutchinson Cancer Research Center, United States
© 2022, Astorga-Gamaza et al.
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