{
  "abstract": "The innate immune system functions as the frontline barrier against invading pathogens, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nevertheless, the virus has developed various strategies to effectively regulate host immune responses, particularly through the inhibition of interferon signaling. In this study, we identify the SARS-CoV-2 accessory protein ORF6 as a key inhibitor of interferon gamma (IFNγ) signaling through downregulation of the interferon-induced 35-kDa protein (IFP35). IFP35, an interferon-stimulated gene (ISG) critical for interferon -mediated antiviral response, is significantly upregulated during SARS-CoV-2 infection. Silencing IFP35 via RNA interference enhances viral replication, indicating its antiviral role. Furthermore, we demonstrate that ORF6 associates with IFP35 and accelerates its ubiquitin-proteasome degradation, thereby impairing IFP35's ability to activate IFNγ signaling. These data reveal novel mechanisms used by SARS-CoV-2 to circumvent host immunity, specifically by impairing IFNγ signaling.",
  "abstract_shown": true,
  "affiliations": [
    "Guangzhou National Laboratory Guangzhou China.",
    "Centre for Infection and Immunity Studies (CIIS), School of Medicine Shenzhen Campus of Sun Yat-sen University Shenzhen China.",
    "Guizhou University of Traditional Chinese Medicine Guiyang China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lihong Liu",
      "orcid": "0009-0006-5863-8754"
    },
    {
      "affs": [
        1
      ],
      "name": "Jie Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiacheng Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Sidi Yang",
      "orcid": "0000-0003-0251-0162"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiaoqiao Xiao"
    },
    {
      "affs": [
        1
      ],
      "name": "Liu Cao"
    },
    {
      "affs": [
        1
      ],
      "name": "Hong Peng"
    },
    {
      "affs": [
        0
      ],
      "name": "Birong Zheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Chunmei Li",
      "orcid": "0000-0002-4034-978X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Deyin Guo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/85c4zjbv37aj1.bib",
  "cited_by": 0,
  "doi": "10.1002/mlf2.70112",
  "fulltext_url": "https://europepmc.org/articles/PMC13710829",
  "id": "85c4zjbv37aj1",
  "issns": [
    "2097-1699",
    "2770-100X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948185",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7223970103",
  "pdf_url": "https://europepmc.org/articles/PMC13710829?pdf=render",
  "pmcid": "PMC13710829",
  "pmid": "42948185",
  "published": "2026-10-26",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/85c4zjbv37aj1.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42948185",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948185"
    },
    {
      "first_seen": "2026-10-31T12:21:43Z",
      "native_id": "PMC13710829",
      "source": "pmc",
      "url": "https://doi.org/10.1002/mlf2.70112"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "SARS-CoV-2 ORF6 protein targets IFP35 to inhibit the IFNγ signaling pathway.",
  "title_text": "SARS-CoV-2 ORF6 protein targets IFP35 to inhibit the IFNγ signaling pathway.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:21Z",
  "url": "https://research.draconitic.com/paper/85c4zjbv37aj1",
  "venue": "MLife",
  "versions": []
}