{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T13:39:57Z","timestamp":1792330797761,"version":"4.4.0"},"reference-count":90,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>HIV\u2010associated neurological complications remain a major concern in people living with HIV (PWH), even under effective viral suppression with combination antiretroviral therapy (cART), underscoring unresolved mechanisms driving HIV\u2010related neurodegeneration. To address this gap, we used HIV\u20101\u2010infected human cerebral organoids (hCOs) containing microglia as a physiologically relevant three\u2010dimensional model of the central nervous system (CNS) and validated key findings in the brain region of simian immunodeficiency virus (SIV)\u2010infected, cART\u2010treated rhesus macaque model. Integrated single\u2010nucleus RNA sequencing with ATAC\u2010seq (multi\u2010omics), identifies cell\u2010type\u2010specific alterations in dual innate immune\u2010driven inflammatory signaling pathways across neural and glial populations in hCOs. Microglia were preferentially infected and activated, initiating IL\u201017A\u2013mediated cascades involving IFN\u2010\u03b3\/STAT1, CEBPB, and NF\u2010\u03baB signaling. These pathways converged with cGAS\u2010STING and Notch\u2013NEURL1 signaling, both associated with neuroinflammation and synaptic dysfunction. cART suppressed viral replication, reduced IL\u201017A\u2010mediated neuroinflammation, improved mitochondrial function, and restored synaptic gene expression. Collectively, these findings identify dysregulation of IL\u201017A, STAT1, CEBPB, and cGAS\u2010STING signaling as key molecular drivers of HIV\u2010associated neuroinflammation. They also establish a potential mechanistic link between IL\u201017A signaling and microglial remodeling, providing a translational framework for the development of CNS\u2010targeted therapies in PWH.<\/jats:p>","DOI":"10.1002\/advs.77954","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:41:13Z","timestamp":1792327273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Signatures of HIV\u2010Induced Neuroinflammation and Neurodegeneration in Human Cerebral Organoids: Identification of Therapeutic Targets for NeuroHIV"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-2646","authenticated-orcid":false,"given":"Karthick","family":"Chennakesavan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Irma Lerma Rangel College of Pharmacy Texas A&amp;M University College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malaroviyam","family":"Samikkannu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Irma Lerma Rangel College of Pharmacy Texas A&amp;M University College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-9862","authenticated-orcid":false,"given":"Shreyan","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olasunkanmi Israel","family":"Tayo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience College of Medicine University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2721-1062","authenticated-orcid":false,"given":"Arpan","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience College of Medicine University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8081-6725","authenticated-orcid":false,"given":"James J.","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6889-4640","authenticated-orcid":false,"given":"Siddappa N.","family":"Byrareddy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience College of Medicine University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-056X","authenticated-orcid":false,"given":"Thangavel","family":"Samikkannu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Irma Lerma Rangel College of Pharmacy Texas A&amp;M University College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_10_2_1","article-title":"Global HIV Targets: A Roadmap to 2030 and Beyond","author":"Global Task Team on HIV Targets Beyond 2025","year":"2025","journal-title":"The Lancet"},{"issue":"5","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0324360","article-title":"Viral Kinetics Among Persons Living With HIV (PLWH) on Dolutegravir\u2010Based Antiretroviral Regimen: A Retrospective and Prospective Analysis from Selected HIV Clinics in Ghana","volume":"20","author":"Badu Nyarko S.","year":"2025","journal-title":"PLoS ONE"},{"issue":"4","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrneurol.2016.27","article-title":"HIV\u2010Associated Neurocognitive Disorder \u2014 Pathogenesis and Prospects for Treatment","volume":"12","author":"Saylor D.","year":"2016","journal-title":"Nature Reviews Neurology"},{"issue":"7879","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41586-021-03209-8","article-title":"Single\u2010Cell Epigenomics Reveals Mechanisms of Human Cortical Development","volume":"598","author":"Ziffra R. 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