論文 - 詳細
| RRC ID | 88135 |
|---|---|
| 著者 | Zhang Y, Samuelson AV. |
| タイトル | Aging impairs the antiviral defense in Caenorhabditis elegans due to loss of DRH-1/RIG-I deSUMOylation by ULP-4/SENP7. |
| ジャーナル | EMBO Rep |
| Abstract |
Innate immune defense relies on post-translational modifications (PTMs) to protect against viral infections. SUMOylation plays complex roles in viral replication and antiviral defenses in mammals and has been implicated in age-associated diseases. Whether PTMs and SUMOylation contribute to age-induced immunosenescence is unknown. We find that antiviral defense in Caenorhabditis elegans is regulated through SUMOylation of DRH-1, ortholog of the cytosolic pattern recognition receptor RIG-I. The SUMO isopeptidase ULP-4 is essential for deSUMOylation of DRH-1 and activation of the intracellular pathogen response (IPR) after exposure to Orsay virus (OV). ULP-4 stabilizes DRH-1, which translocates to the mitochondria to activate the IPR. Loss of drh-1 or ulp-4 compromises antiviral defense; mutant animals fail to clear OV and develop intestinal pathogenesis. During aging, ulp-4 expression decreases, which promotes DRH-1 proteosomal degradation and IPR loss. Mutating the DRH-1 SUMOylated lysines partially rescued the age-associated lost inducibility of the IPR. Our work establishes that aging results in dysregulated SUMOylation and loss of DRH-1, which compromises antiviral defense and creates a physiological shift to favor chronic pathological infection in older animals. |
| 巻・号 | 26(22) |
| ページ | 5459-5482 |
| 公開日 | 2025-11-1 |
| DOI | 10.1038/s44319-025-00589-0 |
| PII | 10.1038/s44319-025-00589-0 |
| PMID | 41039133 |
| PMC | PMC12635358 |
| MeSH | Aging* / genetics Aging* / immunology Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / immunology Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / virology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Immunity, Innate Nodaviridae / immunology Protein Processing, Post-Translational Sumoylation |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm2723 tm3688 |