Scholarlink

<p>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 <i>Caenorhabditis elegans</i> 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 <i>drh-1</i> or <i>ulp-4</i> compromises antiviral defense; mutant animals fail to clear OV and develop intestinal pathogenesis. During aging, <i>ulp-4</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Aging impairs the antiviral defense in Caenorhabditis elegans due to loss of DRH-1/RIG-I deSUMOylation by ULP-4/SENP7

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月2日

查看全文
  • Yun Zhang,
  • Andrew V Samuelson

摘要

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.