|Public on Sep 24, 2023
|The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency [Array]
|Expression profiling by array
|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.
|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.
|Sep 19, 2023
|Last update date
|Nov 24, 2023
|Hannah Sabeth Sperber
|Essen University Hospital
|Institute for transaltional HIV Research
|nCounter Vantage 3D RNA:Protein Immune Cell Profiling Assay
|This SubSeries is part of SuperSeries:
|The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency