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NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control

Authors: Nerea Sánchez-Gaona; Ana Gallego-Cortés; Antonio Astorga-Gamaza; Norma Rallón; José Miguel Benito; Ezequiel Ruiz-Mateos; Adrian Curran; +6 Authors

NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control

Abstract

Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells. Functional analyses indicated that ECs had limited production of functional molecules upon NK stimulation and consequently reduced natural cytotoxicity against non-HIV target cells. Importantly, ECs showed an exceptional ability to kill primary HIV-infected cells by the antibody-dependent cell cytotoxicity adaptive mechanism, which was achieved by a specific memory-like NK population expressing CD16, NKG2A, NKG2C, CD57, and CXCR3. In-depth single-cell RNA-seq unveiled a unique transcriptional signature in these NK cells linked to increased cell metabolism, migration, chemotaxis, effector functions, cytokine secretion, and antiviral response. Our findings underscore a pivotal role of NK cells in the immune control of HIV and identify specific NK cells as emerging targets for immunotherapies.

Keywords

Male, Adult, Receptors, CXCR3, PHENOMENA AND PROCESSES::Microbiological Phenomena::Virus Physiological Phenomena::Virus Replication, HIV Infections, GPI-Linked Proteins, Virus Replication, CD57 Antigens, DISEASES::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections, Immunitat natural, Humans, FENÓMENOS Y PROCESOS::fenómenos microbiológicos::fenómenos fisiológicos de los virus::replicación viral, ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::células asesinas naturales, Other subheadings::Other subheadings::Other subheadings::/immunology, ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH, Receptors, IgG, Antibody-Dependent Cell Cytotoxicity, Middle Aged, Infeccions per VIH - Tractament, ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural, Killer Cells, Natural, Otros calificadores::Otros calificadores::Otros calificadores::/inmunología, HIV-1, Female, Cèl·lules K, NK Cell Lectin-Like Receptor Subfamily C, Research Article

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Top 10%
Average
Top 10%
Green
gold