{
  "abstract": "HIV-associated 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-related neurodegeneration. To address this gap, we used HIV-1-infected human cerebral organoids (hCOs) containing microglia as a physiologically relevant three-dimensional model of the central nervous system (CNS) and validated key findings in the brain region of simian immunodeficiency virus (SIV)-infected, cART-treated rhesus macaque model. Integrated single-nucleus RNA sequencing with ATAC-seq (multi-omics), identifies cell-type-specific alterations in dual innate immune-driven inflammatory signaling pathways across neural and glial populations in hCOs. Microglia were preferentially infected and activated, initiating IL-17A-mediated cascades involving IFN-γ/STAT1, CEBPB, and NF-κB signaling. These pathways converged with cGAS-STING and Notch-NEURL1 signaling, both associated with neuroinflammation and synaptic dysfunction. cART suppressed viral replication, reduced IL-17A-mediated neuroinflammation, improved mitochondrial function, and restored synaptic gene expression. Collectively, these findings identify dysregulation of IL-17A, STAT1, CEBPB, and cGAS-STING signaling as key molecular drivers of HIV-associated neuroinflammation. They also establish a potential mechanistic link between IL-17A signaling and microglial remodeling, providing a translational framework for the development of CNS-targeted therapies in PWH.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, Texas, USA.",
    "Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.",
    "Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Karthick Chennakesavan",
      "orcid": "0000-0003-3538-2646"
    },
    {
      "affs": [
        0
      ],
      "name": "Malaroviyam Samikkannu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shreyan Gupta",
      "orcid": "0000-0002-1904-9862"
    },
    {
      "affs": [
        2
      ],
      "name": "Olasunkanmi Israel Tayo"
    },
    {
      "affs": [
        2
      ],
      "name": "Arpan Acharya",
      "orcid": "0000-0003-2721-1062"
    },
    {
      "affs": [
        1
      ],
      "name": "James J Cai",
      "orcid": "0000-0002-8081-6725"
    },
    {
      "affs": [
        2
      ],
      "name": "Siddappa N Byrareddy",
      "orcid": "0000-0002-6889-4640"
    },
    {
      "affs": [
        0
      ],
      "name": "Thangavel Samikkannu",
      "orcid": "0000-0001-5071-056X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1hzaygr7623y4.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77954",
  "fulltext_url": "https://europepmc.org/articles/PMC13676815",
  "id": "1hzaygr7623y4",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893406",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7222887059",
  "pdf_url": "https://europepmc.org/articles/PMC13676815?pdf=render",
  "pmcid": "PMC13676815",
  "pmid": "42893406",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1hzaygr7623y4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42893406",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893406"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2406|HIV Research and Treatment",
      "subfield": "microbiology"
    }
  ],
  "title": "Molecular Signatures of HIV-Induced Neuroinflammation and Neurodegeneration in Human Cerebral Organoids: Identification of Therapeutic Targets for NeuroHIV.",
  "title_text": "Molecular Signatures of HIV-Induced Neuroinflammation and Neurodegeneration in Human Cerebral Organoids: Identification of Therapeutic Targets for NeuroHIV.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/1hzaygr7623y4",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}