{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:15:19Z","timestamp":1788894919871,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA059876, R01DA054526, R01DA052255"],"award-info":[{"award-number":["R01DA059876, R01DA054526, R01DA052255"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["RF1MH141600, R01MH134319"],"award-info":[{"award-number":["RF1MH141600, R01MH134319"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Chronic inflammation is a hallmark of many diseases, including persistent viral infections. In human immunodeficiency virus (HIV) infection, sustained immune activation contributes to end-organ damage and non-AIDS comorbidities, even during antiretroviral therapy. This mini-review examines the role of Pannexin-1 (PANX1) channel\u2013mediated ATP signaling as a key mechanism of immune communication driving chronic inflammation in HIV infection. Viral engagement of host receptors, such as CD4 and CXCR4, induces PANX1 channel opening in infected or stressed cells, leading to the release of extracellular ATP. Extracellular ATP acts as a danger-associated molecular pattern (DAMP) that engages purinergic receptors. Activation of P2X7 initiates potassium efflux, NLRP3 inflammasome assembly, and caspase-1 cleavage, leading to the maturation of the pro-inflammatory cytokines IL-1\u03b2 and IL-18. The review integrates findings from cellular, molecular, and neuroimmunologic studies to highlight how this PANX1\u2013ATP\u2013P2X7 axis amplifies intercellular communication and propagates chronic immune activation. By positioning HIV as a model system, we discuss how insights from this pathway may extend to other chronic inflammatory conditions. Finally, we explore therapeutic opportunities for targeting PANX1 channels or purinergic receptors to reduce inflammasome-driven pathology. Understanding the mechanisms by which extracellular ATP coordinates immune cell signaling provides a framework for decoding chronic inflammation and designing precision interventions to restore immune balance.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1836368","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:24:07Z","timestamp":1777523047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pannexin-1\u2013mediated ATP signaling as a driver of immune communication and chronic inflammation in HIV infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Emma K.","family":"Kaufman","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia 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