KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir

• DOI: 10.1016/j.xcrm.2023.101202
• Publication Date: 2023-09-22T14:28:59Z
• Authors: Antonio Astorga-G...; David Perea; Nerea Sanchez-Gaona; Marta Calvet-Mira...; Ana Gallego-Cortés; Judith Grau-Expósito; Ildefonso Sanchez...; Joan Rey; Josep Castellví; Adrian Curran; Joaquin Burgos; Jordi Navarro; Paula Suanzes; Vicenç Falcó; Meritxell Genescà; Enrique Martín-Gayo; Maria J. Buzon
• Keywords: :virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH [ENFERMEDADES]; HIV Infections; :Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Killer Cells, Natural [ANATOMY]; :aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos [COMPUESTOS QUÍMICOS Y DROGAS]; Article; 3. Good health; Virus Latency; Killer Cells, Natural; :Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic [CHEMICALS AND DRUGS]; HIV-1; :células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::células asesinas naturales [ANATOMÍA]; Humans; Infeccions per VIH; Receptors cel·lulars; Lectins, C-Type; :Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [DISEASES]; Receptors, Immunologic; Cèl·lules K

Human immunodeficiency virus (HIV) infection induces immunological dysfunction, which limits the elimination of HIV-infected cells during treated infection. Identifying and targeting dysfunctional immune might help accelerate purging persistent viral reservoir. Here, we show that chronic HIV increases natural killer (NK) cell populations expressing negative regulator KLRG1, both in peripheral blood lymph nodes. Antiretroviral treatment (ART) does not reestablish these functionally impaired NK populations, expression KLRG1 correlates with active transcription. Targeting specific antibodies significantly restores capacity to kill cells, reactivates latent present CD4+ T co-expressing reduces intact genomes samples from ART-treated individuals. Our data support potential use immunotherapy against receptor impact reservoir persistence.