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| Item Type: | Article |
|---|---|
| Title: | Identification of drug candidates targeting monocyte reprogramming in people living with HIV |
| Creators Name: | Knoll, R., Bonaguro, L., Dos Santos, J.C., Warnat-Herresthal, S., Jacobs-Cleophas, M.C.P., Blümel, E., Reusch, N., Horne, A., Herbert, M., Nuesch-Germano, M., Otten, T., van der Heijden, W.A., van de Wijer, L., Shalek, A.K., Händler, K., Becker, M., Beyer, M.D., Netea, M.G., Joosten, L.A.B., van der Ven, A.J.A.M., 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 |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media SA |
| Volume: | 14 |
| 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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