{
  "abstract": "The positive transcription elongation factor b (P-TEFb) is a critical host factor for HIV transcription, yet pharmacological inhibition of its CDK9 subunit yields transient suppression with cytotoxicity. We identify that the integrator-PP2A complex enhances the potency and durability of CDK9 inhibition without added toxicity. Activation of PP2A with the small-molecule SMAP-2, combined with a low dose of the CDK9 inhibitor AZD4573, suppresses HIV transcription in CD4⁺ T cells, persisting for 7 days after drug withdrawal. Mechanistically, the drug combination increases integrator recruitment and repressive chromatin marks, decreases RNA polymerase II occupancy and C-terminal domain (CTD) phosphorylation at HIV promoter, and reduces short and long HIV transcripts, without global T cell activation, proliferation or broad transcriptome changes. The drug combination's HIV-inhibiting effect is somewhat resistant against elevated HIV activity in the presence of cocaine or morphine. These findings reveal cooperative P-TEFb inhibition and integrator activation as a promising strategy for durable HIV silencing.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Zichong Li"
    },
    {
      "name": "Francisco J. Zapatero-Belinchón"
    },
    {
      "name": "Patrik Geleziunas"
    },
    {
      "name": "Melanie Ott"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bav3rct29c9d9.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117894",
  "fulltext_url": "https://europepmc.org/articles/PMC13695381",
  "id": "bav3rct29c9d9",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03277-3",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Cell biology"
    ],
    [
      "heading",
      "Microbiology"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7222807989",
  "pdf_url": "https://europepmc.org/articles/PMC13695381?pdf=render",
  "pmcid": "PMC13695381",
  "pmid": "42927123",
  "published": "2026-10-17",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/bav3rct29c9d9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117894",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03277-3"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117894",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226032773"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927123",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "heading:Microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "“Locking” CDK9 inhibition by activating integrator function in HIV transcription",
  "title_text": "“Locking” CDK9 inhibition by activating integrator function in HIV transcription",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/bav3rct29c9d9",
  "venue": "iScience",
  "versions": []
}