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| Status |
Public on Sep 28, 2023 |
| Title |
The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for HIV infection. Here, we implement a systems approach to discover molecular signatures of HIV latently-infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV cure strategies targeting the hypoxia-CD73-adenosine axis.
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| Overall design |
Relatively little is known about the relevance and function of CD73 in human CD4+ T cells. To address this gap, the transcriptome of blood-derived, primary CD73+ and CD73- CD4+ T cells was characterized by RNA sequencing. To that purpose, CD73-/+ cells were isolated from primary CD4+ T cells by fluorescence-activated cell sorting and analyzed by RNA sequencing.
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| Contributor(s) |
Sperber HS |
| Citation(s) |
37910505 |
| |
| Submission date |
Sep 27, 2023 |
| Last update date |
Nov 24, 2023 |
| Contact name |
Hannah Sabeth Sperber |
| E-mail(s) |
Hannahsperber.7@gmail.com
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| Organization name |
Essen University Hospital
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| Department |
Institute for transaltional HIV Research
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| Lab |
Schwarzer Lab
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| Street address |
Virchowstr. 171
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| City |
Essen |
| State/province |
NRW |
| ZIP/Postal code |
45147 |
| Country |
Germany |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE244193 |
The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency |
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| Relations |
| BioProject |
PRJNA1021624 |
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