The hypoxia-regulated ectonucleotidase CD73 is a host determinant of HIV latency.

Autor:	Sperber HS; Vitalant Research Institute, San Francisco, CA, USA; Free University of Berlin, Institute of Biochemistry, Berlin, Germany; University of California, San Francisco, San Francisco, CA, USA; University Hospital Essen, Institute for Translational HIV Research, Essen, Germany., Raymond KA; Vitalant Research Institute, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA., Bouzidi MS; Vitalant Research Institute, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA., Ma T; University of California, San Francisco, San Francisco, CA, USA; Gladstone Institutes, San Francisco, CA, USA., Valdebenito S; The University of Texas Medical Branch, Galveston, TX, USA., Eugenin EA; The University of Texas Medical Branch, Galveston, TX, USA., Roan NR; University of California, San Francisco, San Francisco, CA, USA; Gladstone Institutes, San Francisco, CA, USA., Deeks SG; University of California, San Francisco, San Francisco, CA, USA., Winning S; University of Duisburg-Essen, Institute for Physiology, Essen, Germany., Fandrey J; University of Duisburg-Essen, Institute for Physiology, Essen, Germany., Schwarzer R; University Hospital Essen, Institute for Translational HIV Research, Essen, Germany. Electronic address: roland-schwarzer@gmx.de., Pillai SK; Vitalant Research Institute, San Francisco, CA, USA; University of California, San Francisco, San Francisco, CA, USA. Electronic address: satish.pillai@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Nov 28; Vol. 42 (11), pp. 113285. Date of Electronic Publication: 2023 Oct 31.
DOI:	10.1016/j.celrep.2023.113285
Abstrakt:	Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu