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狂犬病病毒（Rabies virus， RABV）是一种高度致死性人畜共患病病毒，其致病机制尚未完全明确。干扰素诱导的跨膜蛋白3（interferon-induced transmembrane protein 3， IFITM3）作为广谱抗病毒分子，在抗RABV感染中发挥重要作用。IFITM3可发生泛素化途径降解进而参与病毒的复制，但其泛素化-去泛素化修饰稳态尚未有研究报道。因此，探讨IFITM3去泛素化修饰及对病毒复制的影响具有重要意义。本研究通过Co-IP、WB等实验，明确了在HEK-293细胞中IFITM3存在K63链型多聚泛素化修饰，且去泛素化酶USP5为其关键去泛素化调控因子。机制上USP5通过与IFITM3相互作用，特异性去除其K63链型多聚泛素化修饰，提高IFITM3的蛋白稳定性，最终抑制RABV的复制。本研究揭示了在HEK-293细胞中USP5调控IFITM3泛素化修饰的调控机制，为狂犬病的救治提供了新靶点。
Abstract：Rabies virus (RABV) is a highly lethal zoonotic virus， and its pathogenic mechanism has not been fully clarified. Interferon-induced transmembrane protein 3 (IFITM3)， as a broad-spectrum antiviral molecule， plays an important role in resisting RABV infection. IFITM3 can undergo degradation through the ubiquitination pathway and thus participate in viral replication， but the homeostasis of its ubiquitination-deubiquitination modification has not been reported. Therefore， it is of great significance to explore the deubiquitination modification of IFITM3 and its impact on viral replication. In this study， through experiments such as Co-IP and WB， it was confirmed that IFITM3 has K63-linked polyubiquitination modification in HEK-293 cells， and the deubiquitinase USP5 is its key deubiquitination regulatory factor. Mechanistically， USP5 interacts with IFITM3， specifically removes its K63-linked polyubiquitination modification， improves the protein stability of IFITM3， and ultimately inhibits the replication of RABV. This study reveals the regulatory mechanism of USP5 in regulating the ubiquitination modification of IFITM3 in HEK-293 cells， providing a new target for the treatment of rabies.
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基本信息:
中图分类号:S852.65
引用信息:
[1]柳艳彬,王洁,涂长春,等.去泛素化酶（USP5）通过IFITM3蛋白调节狂犬病病毒复制的机制[J].经济动物学报().
基金信息:
国家自然科学基金项目（3227190179）; 病原微生物生物安全全国重点实验室自主研究课题（SKLPBS2407）
2026-03-24
2026-03-24
2026-03-24