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Series GSE243577 Query DataSets for GSE243577
Status Public on Sep 24, 2023
Title The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency [Array]
Organism Homo sapiens
Experiment type Expression profiling by array
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.
Overall design Blood-derived primary CD4+T cells obtained from six healthy individuals were activated in vitro via αCD3/αCD28 bead stimulation and infected with a recombinant HIV dual-reporter virus HIVDFII via spinoculation. Four days post infection, productively- and latently-infected, as well as uninfected cells were purified by fluorescence activated cell sorting. The sorted populations and respective control specimens (untreated samples; unstimulated, infected cells; and stimulated cells without HIVDFII infection) were subsequently subjected to downstream analysis using NanoString hybridization and fluorescence-based digital counting technology allowing for simultaneous detection of 770 mRNA and 30 protein targets.
Contributor(s) Sperber HS
Citation(s) 37910505
Submission date Sep 19, 2023
Last update date Nov 24, 2023
Contact name Hannah Sabeth Sperber
Organization name Essen University Hospital
Department Institute for transaltional HIV Research
Lab Schwarzer Lab
Street address Virchowstr. 171
City Essen
State/province NRW
ZIP/Postal code 45147
Country Germany
Platforms (1)
GPL33774 nCounter Vantage 3D RNA:Protein Immune Cell Profiling Assay
Samples (35)
GSM7791299 hCD4_ACT_rep1
GSM7791300 hCD4_HIVinf_rep1
GSM7791301 hCD4_untreated_rep1
This SubSeries is part of SuperSeries:
GSE244193 The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency
BioProject PRJNA1018954

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Supplementary file Size Download File type/resource
GSE243577_RAW.tar 350.0 Kb (http)(custom) TAR (of RCC)

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