{
  "abstract": "Combination antiretroviral therapy (cART) successfully suppresses systemic HIV-1 replication, yet latent reservoirs persist in long-lived memory CD4+ T cells, myeloid lineages, and specialized anatomical sanctuaries. While previous immunometabolic studies have documented altered bioenergetic profiles in infected host cells, the upstream signaling mechanisms that govern these metabolic states and drive viral fate remain incompletely defined. Here, we present a comprehensive framework positioning intracellular immunometabolic signaling networks—specifically PI3K–AKT–mTOR, AMPK, and HIF-1α—as central transducers linking extracellular microenvironmental signals to cellular bioenergetics, epigenetic remodeling, and viral persistence. We evaluate how the interplay between mTOR-, AMPK-, and HIF-1α-associated signaling influences metabolic and transcriptional states that may shape the balance between active viral expression and deep transcriptional latency. Furthermore, we examine how oxygen-sensing through HIF-1α, tissue-specific nutrient microenvironments (in GALT, lymph nodes, and the CNS), and mitochondrial ROS signaling shape reservoir longevity, clonal expansion, and resistance to apoptosis. Finally, we discuss therapeutic strategies, contrasting traditional \"shock and kill\" approaches with \"metabolically reprogram and kill\" modalities designed to lower the threshold for latency reversal. Understanding and therapeutically manipulating the signaling–metabolism–latency axis may provide new strategies for disrupting viral reservoirs and promoting durable HIV remission.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Samuel Long",
      "orcid": "0000-0001-7559-3232"
    },
    {
      "name": "Abigail Long"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e4gazvfg03987.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008868/v1",
  "fulltext_url": null,
  "id": "e4gazvfg03987",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008868/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7213326771",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008868/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/e4gazvfg03987.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15008868",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008868/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2406|HIV Research and Treatment",
      "subfield": "microbiology"
    }
  ],
  "title": "Immunometabolic Signaling Networks in HIV Persistence: From Cellular Metabolism to Reservoir Control",
  "title_text": "Immunometabolic Signaling Networks in HIV Persistence: From Cellular Metabolism to Reservoir Control",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/e4gazvfg03987",
  "venue": "ChemRxiv",
  "versions": []
}