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TOLLIP inhibits the replication of PEDV by autophagic degradation of Nsp9

文献类型： 外文期刊

作者： Li, Yahui 1 ; Zhang, Yutao 3 ; Cheng, Jiexi 3 ; Chen, Jinyang 4 ; Lin, Zhiwei 4 ; Hu, Boli 3 ; Li, Bin 2 ; Yang, Xianghong 1 ;

作者机构： 1.Zhejiang Prov Peoples Hosp, Hangzhou Med Coll, Affiliated Peoples Hosp, Emergency & Crit Care Ctr,Intens Care Unit, Hangzhou 310014, Peoples R China

2.Minist Agr, Inst Vet Med, Jiangsu Acad Agr Sci, Key Lab Vet Biol Engn & Technol, Nanjing 210014, Peoples R China

3.Zhejiang Univ, Ctr Vet Sci, MOA Key Lab Anim Virol, Hangzhou 310058, Peoples R China

4.Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Clin Res Inst, Hangzhou Med Coll, Hangzhou 310014, Peoples R China

关键词： Autophagy cargo receptors; PEDV; TOLLIP; Selective autophagy; LC3A

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2025 年 304 卷

页码：

收录情况： SCI

摘要： Selective autophagy plays a crucial role in innate antiviral immunity by targeting essential viral components and host factors necessary for virus propagation. Among these factors, the nonstructural protein 9 (Nsp9) of Porcine Epidemic Diarrhea Virus (PEDV) is required for viral replication. However, the host factors regulating Nsp9 have remained elusive. In our study, we discovered that Nsp9 undergoes degradation through selective autophagy. Using coimmunoprecipitation combined with mass spectrometry analysis, we identified Toll-interacting protein (TOLLIP) as an autophagy cargo receptor binding to Nsp9 and facilitating its autophagic degradation. Additionally, we found that TOLLIP interacts with LC3A, LC3C, and GABARAPL1. Further investigations revealed that Nsp9 specifically enhances the binding of TOLLIP to LC3A, rather than LC3C or GABARAPL1. Importantly, TOLLIP promotes the engulfment of Nsp9 by LC3A-coated autophagosomes and mediates Nsp9 trafficking to lysosomes, ultimately leading to LC3A-dependent degradation of Nsp9. Consequently, TOLLIP suppresses PEDV replication. Overall, our findings highlight the role of TOLLIP in connecting viral proteins to LC3A-dependent autophagosome, emphasizing its significance in combating viruses through selective autophagy.

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