{
  "abstract": "Chronic hepatitis C virus (HCV) infection frequently leads to liver cancer. To determine the viral factor(s) potentially involved in viral persistence, we focused our work on NS2, a viral protein of unknown function. To assign a role for NS2, we searched for cellular proteins that interact with NS2. Performing a two-hybrid screen on a human liver cDNA library, we found that NS2 interacted with the liver-specific pro-apoptotic CIDE-B protein. Binding specificity of NS2 for CIDE-B was confirmed by cell-free assays associated with colocalization studies and coprecipitation experiments on human endogenous CIDE-B. CIDE-B, a member of the novel CIDE family of apoptosis-inducing factors, has been reported to show strong cell death-inducing activity in its C-terminal domain. We show that this CIDE-B killing domain is involved in the NS2 interaction. NS2 binding was sufficient to inhibit CIDE-B-induced apoptosis because an NS2 deletion mutant unable to interact with CIDE-B in vitro lost its capacity to interfere with CIDE-B cell death activity. Although it has been reported that CIDE-B-induced apoptosis is characterized by mitochondrial localization, the precise apoptotic mechanism remained unknown. Here, we show that CIDE-B induced cell death in a caspase-dependent manner through cytochrome c release from mitochondria. Furthermore, we found that NS2 counteracted the cytochrome c release induced by CIDE-B. In vivo, the CIDE-B protein level was extremely low in adenovirus-infected transgenic mice expressing the HCV polyprotein compared with that in wild-type mice. We suggest that NS2 interferes with the CIDE-B-induced death pathway and participates in HCV strategies to subvert host cell defense.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Lars Erdtmann"
    },
    {
      "name": "Nathalie Franck"
    },
    {
      "name": "Hervé Lerat"
    },
    {
      "name": "Jacques Le Seyec"
    },
    {
      "name": "David Gilot"
    },
    {
      "name": "Isabelle Cannie"
    },
    {
      "name": "Philippe Gripon"
    },
    {
      "name": "Urszula Hibner"
    },
    {
      "name": "Christiane Guguen-Guillouzo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/02kzmscr3f9a2.bib",
  "cited_by": 131,
  "doi": "10.1074/jbc.m209732200",
  "fulltext_url": null,
  "id": "02kzmscr3f9a2",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://hal.science/hal-05784417v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2721|Hepatitis C virus research"
    ]
  ],
  "openalex": "W2092454476",
  "pdf_url": "http://www.jbc.org/article/S0021925819549250/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/02kzmscr3f9a2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "hal-05784417",
      "source": "hal",
      "url": "https://hal.science/hal-05784417v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Protein Kinase Regulation and GTPase Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The Hepatitis C Virus NS2 Protein Is an Inhibitor of CIDE-B-induced Apoptosis",
  "title_text": "The Hepatitis C Virus NS2 Protein Is an Inhibitor of CIDE-B-induced Apoptosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:50Z",
  "url": "https://research.draconitic.com/paper/02kzmscr3f9a2",
  "venue": "Journal of Biological Chemistry",
  "versions": []
}