Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages
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Significance: A major obstacle to the eradication of HIV-1 by combination antiretroviral therapy (cART) is the formation of cellular reservoirs in CD4 + T lymphocytes (carrying latently integrated provirus) and tissue macrophages. Infected macrophages assemble new virions in subcellular vacuoles known as virus-containing compartments (VCC), hiding them from the immune system and, in part, from antiretroviral agents. Here we report that extracellular ATP is capable of inducing the rapid release of virions accumulated in VCC via interaction with the P2X7 receptor and without inducing cell death, whereas the antidepressant agent Imipramine blocks the release. Thus, our study identifies two “druggable” targets affecting the release of stored virions from infected human macrophages that could bear relevance for purging HIV-1 reservoirs in individuals receiving cART.
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P2X7 receptor facilitates virion release from HIV-infected macrophages in an exocytosis-dependent way.
“Controversially to the above-cited beneficial P2X7 receptor-mediated viral elimination, this receptor was described to even facilitate virion release from HIV-infected macrophages in an exocytosis-dependent way [109].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [109]
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- Authors
- Graziano, F., Desdouits, M., Garzetti, L., Podini, P., Alfano, M., Rubartelli, A., Furlan, R., Benaroch, P., & Poli, G.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Institut Curie (FR)
- IRCCS Ospedale San Raffaele (IT)
- Ospedale Policlinico San Martino (IT)
- University of Maryland, Baltimore (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-06-08
- Volume
- 112
- Issue
- 25
- Pages
- E3265-73
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4485148
- OpenAlex
- W1601323025
- Cited by
- 77
- References
- 62
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 9 · 2016: 6 · 2015: 1
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sidaction
- Agence Nationale de la Recherche (ANR-11-LABX-0043)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- extracellular ATP, HIV-1, macrophages, P2X7 receptor, microvesicles, acid sphingomyelinase, imipramine, viral reservoir, monocyte-derived macrophages, Trojan horse
- MeSH terms
- Adenosine Triphosphate, Disease Reservoirs, Humans, Imipramine, Macrophages, Protein Binding, Viral Proteins, Virion, HIV-1, Receptors, Purinergic P2X7
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