The antiviral role of TRIM25 in mammalian embryonic stem cells

Jie Zou; Yuxin Lin; Chunyan Wu; Yao Ji; Xuankai Zhao; Zhan Xu; Jingfei Gong; Zhiyuan Shi; Tianyang Luo; Xiaoling Xie; Yanan Jiang; Qi Tian; Shuqi Zhang; Yanxi Ji; Yuan Li; Zhenyu He; Shuchun Zhang; Liu Cao; Chun-Mei Li; Junyu Wu; Deyin Guo

doi:10.1016/j.virs.2026.07.011

August 2026

. doi: 10.1016/j.virs.2026.07.011

Citation: Jie Zou, Yuxin Lin, Chunyan Wu, Yao Ji, Xuankai Zhao, Zhan Xu, Jingfei Gong, Zhiyuan Shi, Tianyang Luo, Xiaoling Xie, Yanan Jiang, Qi Tian, Shuqi Zhang, Yanxi Ji, Yuan Li, Zhenyu He, Shuchun Zhang, Liu Cao, Chun-Mei Li, Junyu Wu, Deyin Guo. The antiviral role of TRIM25 in mammalian embryonic stem cells .VIROLOGICA SINICA, 2026, 41(4) : 820-831. http://dx.doi.org/10.1016/j.virs.2026.07.011

TRIM25在哺乳动物胚胎干细胞中的抗病毒作用机制

邹洁 ^a ,
林予馨 ^b ,
吴春燕 ^a ,
季瑶 ^a ,
赵炫凯 ^a ,
许展 ^a ,
巩婧妃 ^a ,
石芷鸢 ^a ,
罗天阳 ^a ,
谢小玲 ^a ,
江亚楠 ^a ,
田祺 ^a ,
张淑琪 ^a ,
冀彦锡 ^a ,
李园 ^a ,
何震宇 ^a ,
张舒淳 ^a ,
曹流 ^a,, ,
李春梅 ^a,, ,
吴俊玉 ^a,, ,
郭德银 ^a,b,c,,

a 中山大学(深圳校区), 中山医学院, 热带病防治研究教育部重点实验室;
b 广州国家实验室, 广州国际生物岛;
c 广州医科大学第一附属医院, 广州呼吸健康研究所, 呼吸疾病全国重点实验室

通讯作者： 曹流, caoliu@mail.sysu.edu.cn; 李春梅, lichm8@mail.sysu.edu.cn; 吴俊玉, wujy68@mail.sysu.edu.cn; 郭德银, guo_deyin@gzlab.ac.cn
收稿日期： 2026-01-17
录用日期： 2026-07-28

摘要

哺乳动物胚胎干细胞（ESCs）尽管缺乏功能性干扰素（IFN）信号传导，却对病毒感染具有高度抗性。然而，其抗病毒防御机制的基础尚未完全阐明。本研究探讨了TRIM25——一种已知的IFN依赖性先天性免疫关键驱动因子——在IFN缺陷型小鼠ESCs（mESCs）中的抗病毒功能作用及分子机制。TRIM25在mESCs中展现出广谱抗病毒活性。通过RNAi敲低或CRISPR介导的Trim25基因敲除实验发现，该因子缺失显著促进了EMCV和VSV病毒的复制与传播。从机制层面看，TRIM25在mESCs中的抗病毒活性与IFN产生及基础ISG表达均无关。在病毒感染的mESC中，TRIM25从细胞核转移到细胞质，直接结合病毒RNA，与G3BP1形成细胞质凝聚物，在感染过程中与dsRNA病灶共定位。G3BP1的遗传扰动同样损害了mESC的抗病毒防御，揭示了TRIM25和应激颗粒成分在限制病毒复制方面的重要协同作用。我们的研究将TRIM25确定为ESC中的关键RNA传感效应器，描绘了一个以前未被认识的IFN-非依赖性内在免疫轴，该轴将病毒RNA监测与应激颗粒介导的抑制联系起来，从而扩展了多能细胞自主抗病毒策略的范式。
- TRIM25
- , 胚胎干细胞
- , G3BP1
- , RNA结合蛋白
- , RNA病毒

The antiviral role of TRIM25 in mammalian embryonic stem cells

Jie Zou ^a ,
Yuxin Lin ^b ,
Chunyan Wu ^a ,
Yao Ji ^a ,
Xuankai Zhao ^a ,
Zhan Xu ^a ,
Jingfei Gong ^a ,
Zhiyuan Shi ^a ,
Tianyang Luo ^a ,
Xiaoling Xie ^a ,
Yanan Jiang ^a ,
Qi Tian ^a ,
Shuqi Zhang ^a ,
Yanxi Ji ^a ,
Yuan Li ^a ,
Zhenyu He ^a ,
Shuchun Zhang ^a ,
Liu Cao ^a,, ,
Chun-Mei Li ^a,, ,
Junyu Wu ^a,, ,
Deyin Guo ^a,b,c,,

a. MOE Key Laboratory of Tropical Disease Control, Zhongshan School of Medicine, Sun Yat-sen University Shenzhen Campus, Shenzhen 518197, China;
b. Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou 510320, China;
c. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China

Corresponding author: Liu Cao, caoliu@mail.sysu.edu.cn Chun-Mei Li, lichm8@mail.sysu.edu.cn Junyu Wu, wujy68@mail.sysu.edu.cn Deyin Guo, guo_deyin@gzlab.ac.cn
Received Date: 17 January 2026
Accepted Date: 28 July 2026

Abstract

Mammalian embryonic stem cells (ESCs), despite lacking functional interferon (IFN) signaling, are remarkably resistant to viral infection. However, the mechanistic basis of their antiviral defenses remains incompletely characterized. In this study, we investigated the antiviral functional role and molecular mechanism of tripartite motif-containing protein 25 (TRIM25), a well-known key driver of IFN-dependent innate immunity, in IFN-deficient mouse ESCs (mESCs). TRIM25 exhibited a broad spectrum of antiviral activity in mESCs. RNAi depletion or CRISPR-mediated knockout of TRIM25 markedly enhanced the replication and propagation of both encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV). Mechanistically, the antiviral activity of TRIM25 in mESCs is independent of both IFN production and constitutive ISG expression. In virus-infected mESCs, TRIM25 translocated from the nucleus to the cytoplasm and directly bound viral RNA, where it formed cytoplasmic condensates with GTPase-activating protein-binding protein 1 (G3BP1) that colocalized with dsRNA foci. Genetic perturbation of G3BP1 similarly compromised the antiviral defenses of mESCs, revealing an essential synergism between TRIM25 and stress granule components in restricting viral replication. Our study identifies TRIM25 as a pivotal RNA-sensing effector in ESCs, delineating a previously unrecognized IFN-independent axis of intrinsic immunity that bridges viral RNA surveillance with stress granule-mediated suppression, thereby expanding the paradigm of pluripotent cell-autonomous antiviral strategies.
- TRIM25
- , Embryonic stem cell
- , G3BP1
- , RNA-binding
- , RNA virus

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Electronic Supplementary Material

10.1016j.virs.2026.07.011-ESM.docx