The EBI2 receptor is coexpressed with CCR5 in CD4 + T cells and boosts HIV-1 R5 replication.

Autor:	Guigues A; Institut de Génétique Humaine, CNRS-Université de Montpellier UMR9002., Gimenez S; Institut de Génétique Humaine, CNRS-Université de Montpellier UMR9002., Mettling C; Institut de Génétique Humaine, CNRS-Université de Montpellier UMR9002., Maurel D; ARPEGE Pharmacology Screening Interactome Platform Facility., Doumazane E; Institut de Génomique Fonctionnelle, CNRS-UMR5203, INSERM-U661, Universités Montpellier 1 & 2.; Paris Brain Institute (ICM), Sorbonne Université, INSERM U1127, CNRS UMR7225, Paris, France., Prézeau L; Institut de Génomique Fonctionnelle, CNRS-UMR5203, INSERM-U661, Universités Montpellier 1 & 2., François V; Institut de Génétique Humaine, CNRS-Université de Montpellier UMR9002., Corbeau P; Institut de Génétique Humaine, CNRS-Université de Montpellier UMR9002.; Université de Montpellier.; Centre Hospitalier Universitaire Carémeau, UF d'Immunologie, Nîmes Cedex 9.
Jazyk:	angličtina
Zdroj:	AIDS (London, England) [AIDS] 2024 Aug 01; Vol. 38 (10), pp. 1449-1459. Date of Electronic Publication: 2024 May 20.
DOI:	10.1097/QAD.0000000000003931
Abstrakt:	Objective: CCR5, a G protein-coupled receptor (GPCR), is used by most HIV strains as a coreceptor. In this study, we looked for other GPCR able to modify HIV-1 infection. Design: We analyzed the effects of one GPCR coexpressed with CCR5, EBI2, on HIV-1 replicative cycle. Methods: We identified GPCR expressed in primary CD4 + CCR5 + T cells by multi-RT-qPCR. We studied GPCR dimerization by FRET technology. Cell lines expressing EBI2 were established by transduction with HIV vectors. HIV-1 entry was quantified with virions harboring β-lactamase fused to the viral protein vpr, early and late HIV-1 transcriptions by qPCR, NFkB nuclear activation by immunofluorescence and transfection, and viral production by measuring p24 concentration in culture supernatant by ELISA. Results: We showed that EBI2 is naturally expressed in primary CD4 + CCR5 + T cells, and that CCR5 and EBI2 heterodimerize. We observed that this coexpression reduced viral entry by 50%. The amount of HIV reverse transcripts was similar in cells expressing or not EBI2. Finally, the presence of EBI2 induced the translocation of NFkB and activated HIV-1 genome expression. Globally, the result was a drastic HIV-1 R5, but not X4, overproduction in EBI2 -transduced cells. Conclusion: EBI2 expression in CD4 + CCR5 + cells boosts HIV-1 R5 productive infection. As the natural ligand for EBI2 is present in blood and lymphoid tissues, the constant EBI2 activation might increase HIV replication in CD4 + T cells. It might be of interest to test the effect of EBI2 antagonists on the residual viral production persisting in patients aviremic under treatment. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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