Thioredoxin 2 Is a Novel E2-Interacting Protein That Inhibits the Replication of Classical Swine Fever Virus

文献类型： 外文期刊

第一作者： Li, Su

作者： Li, Su;Wang, Jinghan;He, Wen-Rui;Feng, Shuo;Li, Yongfeng;Wang, Xiao;Liao, Yajin;Qin, Hua-Yang;Li, Lian-Feng;Dong, Hong;Sun, Yuan;Luo, Yuzi;Qiu, Hua-Ji

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期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.103； 五年影响因子：5.078 ）

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收录情况： SCI

摘要： The E2 protein of classical swine fever virus (CSFV) is an envelope glycoprotein that is involved in virus attachment and entry. To date, the E2-interacting cellular proteins and their involvement in viral replication have been poorly documented. In this study, thioredoxin 2 (Trx2) was identified to be a novel E2-interacting partner using yeast two-hybrid screening from a porcine macrophage cDNA library. Trx2 is a mitochondrion-associated protein that participates in diverse cellular events. The Trx2-E2 interaction was further confirmed by glutathione S-transferase (GST) pulldown, in situ proximity ligation, and laser confocal assays. The thioredoxin domain of Trx2 and the asparagine at position 37 (N37) in the E2 protein were shown to be critical for the interaction. Silencing of the Trx2 expression in PK-15 cells by small interfering RNAs significantly promotes CSFV replication, and conversely, overexpression of Trx2 markedly inhibits viral replication of the wild-type (wt) CSFV and to a greater extent that of the CSFV N37D mutant, which is defective in binding Trx2. The wt CSFV but not the CSFV N37D mutant was shown to reduce the Trx2 protein expression in PK-15 cells. Furthermore, we demonstrated that Trx2 increases nuclear factor kappa B (NF-kappa B) promoter activity by promoting the nuclear translocation of the p65 subunit of NF-kappa B. Notably, activation of the NF-kappa B signaling pathway induced by tumor necrosis factor alpha (TNF-alpha) significantly inhibits CSFV replication in PK-15 cells, whereas blocking the NF-kappa B activation in Trx2-overexpressing cells no longer suppresses CSFV replication. Taken together, our findings reveal that Trx2 inhibits CSFV replication via the NF-kappa B signaling pathway.

分类号： Q934.2

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