51. FUBP3 Degrades the Porcine Epidemic Diarrhea Virus Nucleocapsid Protein and Induces the Production of Type I Interferon
- Author
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Sujie Dong, Ning Kong, Chunmei Wang, Youwen Li, Dage Sun, Wenzhen Qin, Huanjie Zhai, Xueying Zhai, Xinyu Yang, Chenqian Ye, Manqing Ye, Changlong Liu, Lingxue Yu, Hao Zheng, Wu Tong, Hai Yu, Wen Zhang, Guangzhi Tong, and Tongling Shan
- Subjects
TNF Receptor-Associated Factor 3 ,Swine ,Porcine epidemic diarrhea virus ,Ubiquitin-Protein Ligases ,Immunology ,Nucleocapsid Proteins ,Microbiology ,Antiviral Agents ,Cell Line ,Virology ,Insect Science ,Chlorocebus aethiops ,Interferon Type I ,Animals ,Coronavirus Infections ,Vero Cells ,Transcription Factors - Abstract
Porcine epidemic diarrhea virus (PEDV) is the globally distributed alphacoronavirus that can cause lethal watery diarrhea in piglets, causing substantial economic damage. However, the current commercial vaccines cannot effectively the existing diseases. Thus, it is of great necessity to identify the host antiviral factors and the mechanism by which the host immune system responds against PEDV infection required to be explored. The current work demonstrated that the host protein, the far upstream element-binding protein 3 (FUBP3), could be controlled by the transcription factor TCFL5, which could suppress PEDV replication through targeting and degrading the nucleocapsid (N) protein of the virus based on selective autophagy. For the ubiquitination of the N protein, FUBP3 was found to recruit the E3 ubiquitin ligase MARCH8/MARCHF8, which was then identified, transported to, and degraded in autolysosomes via NDP52/CALCOCO2 (cargo receptors), resulting in impaired viral proliferation. Additionally, FUBP3 was found to positively regulate type-I interferon (IFN-I) signaling and activate the IFN-I signaling pathway by interacting and increasing the expression of tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3). Collectively, this study showed a novel mechanism of FUBP3-mediated virus restriction, where FUBP3 was found to degrade the viral N protein and induce IFN-I production, aiming to hinder the replication of PEDV.
- Published
- 2022