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| Status |
Public on Jul 30, 2020 |
| Title |
CD4+ T cell transcriptional reprogramming by small compounds |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
A major obstacle for HIV eradication is the persistence of latent reservoirs, cells harboring replication competent yet transcriptionally silent proviruses. These reservoirs, composed primarily of CD4+ T cells, cannot be targeted by the host immune system or by combination anti-retroviral therapy (cART). Upon cessation of cART, a rapid viral rebound occurs. In order to develop effective HIV cure therapies, a better understanding of the factors and host programd governing latency establishment and/or maintenance must be obtained. To achieve this goal, we treated a CD4+T cell-based model of latency (J-Lat 10.6) with Latency Reversing Agents (LRAs) and performed bulk RNA-seq to predict host transcriptional programs activated, and potentially involved, in latent HIV reactivation. Our findings suggest that a novel small molecule (EPH-334) reactivates latent HIV by activating an oxidative stress transcriptional program linked to activation of MAPKs and downstream master regulators. Interestingly, the pan histone deacetylase inhibitor SAHA also induces oxidative stress programs potentially linking sensing of redox state aletartions with activation of cell signaling and transcriptioonal programs culminating on latent HIV reactivation.
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| Overall design |
Steady-state RNA levels were compared between untreated (0hr) and time-course LRA treated J-Lat 10.6 cells. Each data set consists of twelve samples, which are four timepoints each in triplicates. Type of library preparation: Strand Specific Whole Transcriptome.
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| Contributor(s) |
Cruz-Lorenzo E, Lee J, D'Orso I |
| Citation(s) |
35250265, 36298843 |
| |
| Submission date |
Jan 30, 2020 |
| Last update date |
Nov 02, 2022 |
| Contact name |
Ivan D'Orso |
| E-mail(s) |
ivan.dorso@utsouthwestern.edu
|
| Phone |
214-633-1374
|
| Organization name |
UT Southwestern Medical Center
|
| Department |
Microbiology
|
| Lab |
NL3.110A
|
| Street address |
5323 Harry Hines
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9048 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (24)
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| Relations |
| BioProject |
PRJNA604013 |
| SRA |
SRP246167 |
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