{
  "abstract": "Background: Hepatitis B virus (HBV) basal core promoter (BCP) and precore (PC) mutations occur during chronic HBV infection with the BCP-mutant being associated with increased hepatocellular carcinoma (HCC) risk. Objectives: The effects of these mutants on viral replication, hepatocyte biology, and carcinogenesis remain poorly defined. To address this, we characterized BCP- and PC-mutants using human hepatocyte chimeric mice and asked whether the resulting infection-induced transcriptomes correspond to subsets of human HBV-related hepatocellular carcinomas (HBV-HCCs). Design: Isogenic wild-type (WT), BCP- and PC-mutants of HBV genotypes A, C, and D (HBV-A, -C, -D) were generated from recombinant covalently-closed circular DNA to infect chimeric mice. HBV-HCC transcriptomic datasets from The Cancer Genome Atlas (TCGA) were used to stratify association of HBV variants with HCC subtypes. Results: WT, BCP-mutant, and PC-mutant HBV sequences remained genetically stable. The BCP mutation, but not the PC mutation, accelerated the rise in serum viremia in HBV-D- and HBV-A-infected chimeras; in HBV-C, acceleration required both (PC+BCP) mutations. Further comparisons of HBV-D variants revealed that the BCP-mutant increased intrahepatic viral DNA, viral protein expression, and upregulated cancer-related pathways, including transcripts associated with a subset of HBV-HCCs. Analysis of HBV-HCC samples from the TCGA revealed that tumors often harbor a mixture of WT and mutant transcripts, and that WT- and BCP-mutant-associated HCCs exhibit distinct transcriptional profiles. Conclusions: The HBV BCP-mutant directly perturbs hepatocyte homeostasis via virus-intrinsic mechanisms, selectively activating cancer-related pathways and defining a molecularly distinct subset of HBV-HCC. These findings suggest that HBV variants form distinct subcategories of HBV-HCCs.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "L. L. Seifert"
    },
    {
      "name": "G. Dangas"
    },
    {
      "name": "H. Chu"
    },
    {
      "name": "Y. Yu"
    },
    {
      "name": "K. Ogata"
    },
    {
      "name": "X. Hong"
    },
    {
      "name": "M. Zhang"
    },
    {
      "name": "Y. Zhou"
    },
    {
      "name": "C. Zou"
    },
    {
      "name": "A. Ramandi"
    },
    {
      "name": "C. Quirk"
    },
    {
      "name": "E. Moschogianni"
    },
    {
      "name": "C. A. Freije"
    },
    {
      "name": "A. Athanasiadis"
    },
    {
      "name": "L. Gonzales"
    },
    {
      "name": "L. Chiriboga"
    },
    {
      "name": "C. Fulmer"
    },
    {
      "name": "H. Hur"
    },
    {
      "name": "M. Kandpal"
    },
    {
      "name": "A. S. Lok"
    },
    {
      "name": "C. Lareau"
    },
    {
      "name": "W. M. Schneider"
    },
    {
      "name": "C. M. Rice"
    },
    {
      "name": "E. Michailidis"
    },
    {
      "name": "Y. P. de Jong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ac67tg4zwn161.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.752323",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.752323v1.full",
  "id": "ac67tg4zwn161",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.752323v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "2713|Hepatitis B Virus Studies"
    ]
  ],
  "openalex": "W7214078866",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.752323v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ac67tg4zwn161.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:00Z",
      "native_id": "10.64898/2026.09.22.752323",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.752323v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The HBV basal core promoter mutation confers a replicative advantage and transcriptionally reprograms hepatocytes toward HCC subtypes",
  "title_text": "The HBV basal core promoter mutation confers a replicative advantage and transcriptionally reprograms hepatocytes toward HCC subtypes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:00Z",
  "url": "https://research.draconitic.com/paper/ac67tg4zwn161",
  "venue": "bioRxiv",
  "versions": []
}