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

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-10-02 DOI:10.1038/s44319-025-00589-0

Yun Zhang, Andrew V Samuelson

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引用次数: 0

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.

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衰老会损害秀丽隐杆线虫的抗病毒防御，这是由于ULP-4/SENP7失去DRH-1/ rig -1 deSUMOylation。

先天免疫防御依赖于翻译后修饰（PTMs）来保护免受病毒感染。SUMOylation在哺乳动物的病毒复制和抗病毒防御中起着复杂的作用，并与年龄相关的疾病有关。ptm和sumo酰化是否与年龄诱导的免疫衰老有关尚不清楚。我们发现秀丽隐杆线虫的抗病毒防御是通过胞浆模式识别受体rig -1的同源物DRH-1的SUMOylation调节的。暴露于奥赛病毒（OV）后，SUMO异肽酶ULP-4对DRH-1的去umo化和细胞内病原体反应（IPR）的激活至关重要。ULP-4稳定DRH-1， DRH-1易位到线粒体激活IPR。drh-1或ulp-4的缺失损害抗病毒防御；突变动物不能清除OV并发展为肠道发病机制。随着年龄的增长，ulp-4表达减少，促进DRH-1蛋白体降解和IPR丢失。突变DRH-1 SUMOylated赖氨酸部分挽救了与年龄相关的IPR诱导性丧失。我们的研究表明，衰老导致SUMOylation失调和DRH-1的缺失，这损害了抗病毒防御，并在老年动物中产生有利于慢性病理性感染的生理转变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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