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.
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
- Julie M Overbaugh, Fred Hutchinson Cancer Research Center, United States
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.
Metrics
-
- 1,656
- Page views
-
- 280
- Downloads
-
- 8
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response
eLife 11:e78294.
https://doi.org/10.7554/eLife.78294
Further reading
-
- Chromosomes and Gene Expression
- Microbiology and Infectious Disease
African trypanosomes evade host immune clearance by antigenic variation, causing persistent infections in humans and animals. These parasites express a homogeneous surface coat of variant surface glycoproteins (VSGs). They transcribe one out of hundreds of VSG genes at a time from telomeric expression sites (ESs) and periodically change the VSG expressed by transcriptional switching or recombination. The mechanisms underlying the control of VSG switching and its developmental silencing remain elusive. We report that telomeric ES activation and silencing entail an on/off genetic switch controlled by a nuclear phosphoinositide signaling system. This system includes a nuclear phosphatidylinositol 5-phosphatase (PIP5Pase), its substrate PI(3,4,5)P3, and the repressor-activator protein 1 (RAP1). RAP1 binds to ES sequences flanking VSG genes via its DNA binding domains and represses VSG transcription. In contrast, PI(3,4,5)P3 binds to the N-terminus of RAP1 and controls its DNA binding activity. Transient inactivation of PIP5Pase results in the accumulation of nuclear PI(3,4,5)P3, which binds RAP1 and displaces it from ESs, activating transcription of silent ESs and VSG switching. The system is also required for the developmental silencing of VSG genes. The data provides a mechanism controlling reversible telomere silencing essential for the periodic switching in VSG expression and its developmental regulation.
-
- Microbiology and Infectious Disease
- Plant Biology
Purinergic signaling activated by extracellular nucleotides and their derivative nucleosides trigger sophisticated signaling networks. The outcome of these pathways determine the capacity of the organism to survive under challenging conditions. Both extracellular ATP (eATP) and Adenosine (eAdo) act as primary messengers in mammals, essential for immunosuppressive responses. Despite the clear role of eATP as a plant damage-associated molecular pattern, the function of its nucleoside, eAdo, and of the eAdo/eATP balance in plant stress response remain to be fully elucidated. This is particularly relevant in the context of plant-microbe interaction, where the intruder manipulates the extracellular matrix. Here, we identify Ado as a main molecule secreted by the vascular fungus Fusarium oxysporum. We show that eAdo modulates the plant's susceptibility to fungal colonization by altering the eATP-mediated apoplastic pH homeostasis, an essential physiological player during the infection of this pathogen. Our work indicates that plant pathogens actively imbalance the apoplastic eAdo/eATP levels as a virulence mechanism.
