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| Status |
Public on Mar 22, 2018 |
| Title |
HIV-1 infection of human monocyte-derived dendritic cells with and without the integrase inhibitor, Raltegravir (ATAC-Seq). |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Myeloid dendritic cells (DCs) have the innate capacity to sense pathogens and orchestrate immune responses. However, DCs do not mount efficient immune responses to HIV-1, due to potent restriction at the level of reverse transcription. Here, we uncover that when reverse transcription is allowed to proceed, DCs detect HIV-1 in distinct phases, before and after integration. Blocking integration suppressed, but did not abolish, activation of the transcription factor, IRF3, interferon responses, and DC maturation. The cytoplasmic DNA sensor, cGAS, and the E3 ligase, TRIM5, were both required for these responses. Consistent with two stages of innate activation, HIV-1 altered host chromatin accessibility before and after integration. Our studies support the hypothesis that HIV-1 replication increases the amount of material available for sensing and that cGAS signaling can be tuned by discrete inflammatory inputs to drive DC maturation.
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| Overall design |
DCs were derived from the peripheral blood from three deidentified human donors and infected with a single-cycle HIV-1 reporter virus (HIV-GFP) in the presence of Vpx, with and without Raltegravir. At 0, 16, 32, and 48 hours after infection, live cells were sorted and then prepped for an Assay for Transposase-Accessible Chromatin with high-throughput Sequencing (ATAC-Seq).
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| Contributor(s) |
Johnson JS, Amon LM, Aderem A |
| Citation(s) |
29544097 |
| |
| Submission date |
Jun 22, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jarrod S Johnson |
| Organization name |
Center for Infectious Disease Research
|
| Street address |
307 Westlake Ave, Suite 500
|
| City |
Seattle |
| State/province |
Washington |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE100377 |
HIV-1 infection of human monocyte-derived dendritic cells with and without the integrase inhibitor, Raltegravir |
|
| Relations |
| BioProject |
PRJNA391485 |
| SRA |
SRP110173 |
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