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- Title
Identification of drug candidates targeting monocyte reprogramming in people living with HIV.
- Authors
Knoll, Rainer; Bonaguro, Lorenzo; dos Santos, Je´ ssica C.; Warnat-Herresthal, Stefanie; Jacobs-Cleophas, Maartje C. P.; Blümel, Edda; Reusch, Nico; Horne, Arik; Herbert, Miriam; Nuesch-Germano, Melanie; Otten, Twan; van der Heijden, Wouter A.; van de Wijer, Lisa; Shalek, Alex K.; Händler, Kristian; Becker, Matthias; Beyer, Marc D.; Netea, Mihai G.; Joosten, Leo A. B.; van der Ven, Andre J. A. M.
- Abstract
Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers. Methods: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. Results: Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Further, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. Discussion: These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes.
- Subjects
HIV-positive persons; TECHNOLOGICAL innovations; TRANSCRIPTOMES; HIV infections; ANTIRETROVIRAL agents
- Publication
Frontiers in Immunology, 2023, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1275136