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| Status |
Public on Aug 07, 2024 |
| Title |
Transcriptional profiling of antigen-responding CD4 T cells from PLWH to antigenic stimulation or global T cell activation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite antiretroviral therapy (ART), HIV-1 persists in latently-infected CD4+ T cells, preventing cure. Antigen (Ag) drives proliferation of infected cells, preventing latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood since most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4+ T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from participants on long-term ART and assessed T cell activation and HIV-1 RNA expression upon co-culture with autologous dendritic cells (DCs) presenting cognate antigens. Physiological presentation of cognate antigens induced broad T cell activation (median 42-fold increase in CD154+CD69+ cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, physiologic antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity on ART and viral rebound upon ART interruption. Additionally, we observed striking differences in the transcriptome profiles of Ag-responding CD4+ T cells after stimulations with Ag or global T cell activators. This analysis revealed quantitative differences between NFAT and NFkB target genes and may guide future approaches to Ag-mediated HIV-1 latency reversal.
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| Overall design |
Gene expression profiling analysis was performed by using RNA-seq data from 6 study participants with each study participant having antigenic stimlation and global T cell activating treatment.
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| Contributor(s) |
Moskovljevic M, Simonetti FR, Siliciano RF, White JR |
| Citation missing |
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| BioProject |
PRJNA1126650 |
| |
| Submission date |
Aug 02, 2024 |
| Last update date |
Aug 07, 2024 |
| Contact name |
Milica Moskovljevic |
| E-mail(s) |
mmoskov2@jhmi.edu
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| Organization name |
Johns Hopkins University
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| Department |
School of Medicine
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| Lab |
Siliciano Lab
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| Street address |
733 N Baltimore St, Miller Research Building
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (31)
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