Identification of drug candidates targeting monocyte reprogramming in people living with HIV
Published in Frontiers in Immunology, 2023
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.
Recommended citation: Rainer Knoll, Lorenzo Bonaguro, Jéssica C Dos Santos, Stefanie Warnat-Herresthal, Maartje CP Jacobs-Cleophas, Edda Blümel, Nico Reusch, Arik Horne, Miriam Herbert, Melanie Nuesch-Germano, Twan Otten, Wouter A van der Heijden, Lisa van de Wijer, Alex K Shalek, Kristian Händler, Matthias Becker, Marc D Beyer, Mihai G Netea, Leo AB Joosten, Andre JAM van der Ven, Joachim L Schultze, Anna C Aschenbrenner. (2023). "Identification of drug candidates targeting monocyte reprogramming in people living with HIV"." Frontiers in Immunology. 14.
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