Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response

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 ce...

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Bibliographic Details
Published in:eLife 2022-05, Vol.11
Main Authors: Astorga-Gamaza, Antonio, Grau-Expósito, Judith, Burgos, Joaquín, Navarro, Jordi, Curran, Adrià, Planas, Bibiana, Suanzes, Paula, Falcó, Vicenç, Genescà, Meritxell, Buzon, Maria
Format: Article
Language:English
Subjects:
Antibodies
Antigen-antibody complexes
Antiretroviral drugs
Antiretroviral therapy
Antiviral agents
Cytotoxicity
Flow cytometry
Health aspects
Highly active antiretroviral therapy
HIV
HIV (Viruses)
Human immunodeficiency virus
immune resistance
Immune response
Immunoglobulins
Infection
Infections
Ligands
Lymphocytes
Medical equipment and supplies industry
Medical test kit industry
Microbiology and Infectious Disease
Natural killer cells
reservoir
Stem cells
Viral antibodies
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.78294