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Identification of drug candidates targeting monocyte reprogramming in people living with HIV

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Item Type:Article
Title:Identification of drug candidates targeting monocyte reprogramming in people living with HIV
Creators Name:Knoll, R. and Bonaguro, L. and Dos Santos, J.C. and Warnat-Herresthal, S. and Jacobs-Cleophas, M.C.P. and Blümel, E. and Reusch, N. and Horne, A. and Herbert, M. and Nuesch-Germano, M. and Otten, T. and van der Heijden, W.A. and van de Wijer, L. and Shalek, A.K. and Händler, K. and Becker, M. and Beyer, M.D. and Netea, M.G. and Joosten, L.A.B. and van der Ven, A.J.A.M. and Schultze, J.L. and Aschenbrenner, A.C.
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.
Keywords:Systems Immunology, Transcriptomics, HIV, Monocytes, Inflammation, Drug Repurposing
Source:Frontiers in Immunology
Publisher:Frontiers Media SA
Page Range:1275136
Date:20 November 2023
Official Publication:https://doi.org/10.3389/fimmu.2023.1275136
PubMed:View item in PubMed

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