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).
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
-
- 2,000
- views
-
- 315
- downloads
-
- 14
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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
-
- Biochemistry and Chemical Biology
- Microbiology and Infectious Disease
In the bacterium M. smegmatis, an enzyme called MftG allows the cofactor mycofactocin to transfer electrons released during ethanol metabolism to the electron transport chain.
-
- Microbiology and Infectious Disease
Bacterial regional demonstration after global dissemination is an essential pathway for selecting distinct finesses. However, the evolution of the resistome during the transition to endemicity remains unaddressed. Using the most comprehensive whole-genome sequencing dataset of Salmonella enterica serovar Gallinarum (S. Gallinarum) collected from 15 countries, including 45 newly recovered samples from two related local regions, we established the relationship among avian-specific pathogen genetic profiles and localization patterns. Initially, we revealed the international transmission and evolutionary history of S. Gallinarum to recent endemicity through phylogenetic analysis conducted using a spatiotemporal Bayesian framework. Our findings indicate that the independent acquisition of the resistome via the mobilome, primarily through plasmids and transposons, shapes a unique antimicrobial resistance profile among different lineages. Notably, the mobilome-resistome combination among distinct lineages exhibits a geographical-specific manner, further supporting a localized endemic mobilome-driven process. Collectively, this study elucidates resistome adaptation in the endemic transition of an avian-specific pathogen, likely driven by the localized farming style, and provides valuable insights for targeted interventions.
