PTBP1 suppresses porcine epidemic diarrhea virus replication via inducing protein degradation and IFN production
文献类型: 外文期刊
作者: Wenzhen Qin;Ning Kong;Yu Zhang;Chunmei Wang;Sujie Dong;Huanjie Zhai;Xueying Zhai;Xinyu Yang;Chenqian Ye;Manqing Ye;Wu Tong;Changlong Liu;Lingxue Yu;Hao Zheng;Hai Yu;Wen Zhang;Daoliang Lan;Guangzhi Tong;Tongling Shan
作者机构:
关键词: IFN-I;N protein;PEDV;PTBP1;selective autophagy
期刊名称: Journal of Biological Chemistry
ISSN: 0021-9258
年卷期: 2023 年 299 卷 8 期
页码:
收录情况: SCIE(2023版) ; ; EI(2023版)
摘要: Porcine epidemic diarrhea virus (PEDV) causes severe morbidity and mortality among newborn piglets. It significantly threatens the porcine industry in China and around the globe. To accelerate the developmental pace of drugs or vaccines against PEDV, a deeper understanding of the interaction between viral proteins and host factors is crucial. The RNA-binding protein, polypyrimidine tract–binding protein 1 (PTBP1), is crucial for controlling RNA metabolism and biological processes. The present work focused on exploring the effect of PTBP1 on PEDV replication. PTBP1 was upregulated during PEDV infection. The PEDV nucleocapsid (N) protein was degraded through the autophagic and proteasomal degradation pathways. Moreover, PTBP1 recruits MARCH8 (an E3 ubiquitin ligase) and NDP52 (a cargo receptor) for N protein catalysis and degradation through selective autophagy. Furthermore, PTBP1 induces the host innate antiviral response via upregulating the expression of MyD88, which then regulates TNF receptor–associated factor 3/ TNF receptor–associated factor 6 expression and induces the phosphorylation of TBK1 and IFN regulatory factor 3. These processes activate the type Ⅰ IFN signaling pathway to antagonize PEDV replication. Collectively, this work illustrates a new mechanism related to PTBP1-induced viral restriction, where PTBP1 degrades the viral N protein and induces type Ⅰ IFN production to suppress PEDV replication.
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