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

  1. Antonio Astorga-Gamaza

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Judith Grau-Expósito

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Joaquín Burgos

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Jordi Navarro

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7187-0367
  5. Adrià Curran

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Bibiana Planas

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Paula Suanzes

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6871-0098
  8. Vicenç Falcó

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Meritxell Genescà

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Maria Buzon

    Infectious Disease Department, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
    For correspondence
    mariajose.buzon@vhir.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4427-9413

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.

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).

Reviewing Editor

  1. Julie M Overbaugh, Fred Hutchinson Cancer Research Center, United States

Version history

  1. Preprint posted: February 25, 2022 (view preprint)
  2. Received: March 1, 2022
  3. Accepted: May 23, 2022
  4. Accepted Manuscript published: May 26, 2022 (version 1)
  5. 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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  1. Antonio Astorga-Gamaza
  2. Judith Grau-Expósito
  3. Joaquín Burgos
  4. Jordi Navarro
  5. Adrià Curran
  6. Bibiana Planas
  7. Paula Suanzes
  8. Vicenç Falcó
  9. Meritxell Genescà
  10. Maria Buzon
(2022)
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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