{
  "abstract": "Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose accessory proteins have incompletely understood roles in cellular injury. Bioinformatic analysis identified putative N-terminal signal peptides in ORF7a and ORF8. We characterized their expression, subcellular localization, and cytopathic effects in vitro. EGFP-tagged ORF7a and ORF8 showed intracellular ER–Golgi-associated distributions, and untagged ORF7a showed Golgi-associated localization. ORF7a, but not ORF8, induced prominent cytotoxicity in HEK293T cells, as assessed by real-time cell analysis and Annexin V/PI staining. Transcriptomic profiling identified changes in stress-, cell-death-, and ferroptosis-related genes. Ferrostatin-1 attenuated ORF7a-associated cytotoxicity, consistent with ferroptosis-related mechanisms. Mutation of the C-terminal ER retrieval motif (ORF7a-ARA) altered subcellular distribution and attenuated cytotoxicity and cFos/cJun accumulation. The AP-1 inhibitor T-5224 also attenuated cytotoxicity. Additional experiments demonstrated ORF7a localization in A549 cells and extended selected cytotoxicity and inhibitor-response findings to HK-2 cells. In HK-2 cells, ORF7a increased cJun abundance and reduced SLC7A11 and HO-1 protein levels. Together, these findings link the ER retrieval motif to ORF7a-associated cellular injury and support AP-1 involvement and the presence of ferroptosis-related features. Clinical trial number: not applicable.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan",
    "Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan",
    "Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Corresponding author at: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chia-Hsin Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Ru-Fang Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yi-Hsiu Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei-Yu Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aj1gtjpr05j4p.bib",
  "cited_by": 0,
  "doi": "10.1016/j.yexmp.2026.105095",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S0014480026000742",
  "id": "aj1gtjpr05j4p",
  "issns": [
    "1096-0945"
  ],
  "landing_url": "https://doi.org/10.1016/j.yexmp.2026.105095",
  "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": [
    [
      "lcc",
      "RB1-214"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7225083113",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/aj1gtjpr05j4p.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T14:20:46Z",
      "native_id": "05b981dfc1bf403b80a10d35fde66e48",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.yexmp.2026.105095"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "SARS-CoV-2 ORF7a induces cytotoxicity associated with AP-1 signaling and ferroptosis-related responses",
  "title_text": "SARS-CoV-2 ORF7a induces cytotoxicity associated with AP-1 signaling and ferroptosis-related responses",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T14:20:10Z",
  "url": "https://research.draconitic.com/paper/aj1gtjpr05j4p",
  "venue": "Experimental and Molecular Pathology",
  "versions": []
}