TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication.
TRAF6 is a novel NS3-interacting protein that inhibits classical swine fever virus replication.
复制标题
TRAF6 是一种新型 NS3 相互作用蛋白，可抑制猪瘟病毒复制
DOI：
10.1038/s41598-017-06934-1
复制
发表时间：
2017-07-27
影响因子：
4.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Lv H;Dong W;Cao Z;Li X;Wang J;Qian G;Lv Q;Wang C;Guo K;Zhang Y
猪瘟病毒(CSFV)非结构蛋白3(NS3)是一种在病毒复制中起重要作用的多功能非结构蛋白。然而，NS3到底是如何发挥这些功能的尚不清楚。在这里，我们通过酵母双杂交分析、免疫共沉淀和谷胱甘肽-转移酶下拉试验鉴定了肿瘤坏死因子受体相关因子6(TRAF6)是一种新的NS3相互作用蛋白。此外，我们观察到TRAF6过表达显著抑制CSFV在猪肺泡巨噬细胞中的复制，而TRAF6基因敲除则促进CSFV的复制。此外，TRAF6在CSFV感染或NS3单独表达时被降解，表明CSFV和TRAF6是相互拮抗的，TRAF6的降解可能有助于CSFV的持续复制。此外，TRAF6过表达细胞的核因子-κB活性、干扰素-β和白介素6的表达增加，而TRAF6基因敲除细胞的核因子-κB活性、干扰素-β和IL-6水平降低。值得注意的是，在p65基因敲除抑制了NF-κB的激活后，TRAF6的过表达并没有减少猪瘟病毒的复制。我们的研究结果表明，TRAF6通过激活NF-κB信号通路以及增加其靶标干扰素-β和IL-6的表达来抑制猪瘟病毒的复制。这项工作涉及CSFV感染过程中先天抗病毒免疫反应调节的一个新方面。
Classical swine fever virus (CSFV) non-structural protein 3 (NS3) is a multifunctional non-structural protein that plays a major role in viral replication. However, how exactly NS3 exerts these functions remains unknown. Here, we identified tumour necrosis factor receptor-associated factor 6 (TRAF6) as a novel NS3-interacting protein via yeast two-hybrid analysis, co-immunoprecipitation, and glutathioneS-transferase pull-down assays. Furthermore, we observed that TRAF6 overexpression significantly inhibited CSFV replication, and TRAF6 knockdown promoted CSFV replication in porcine alveolar macrophages. Additionally, TRAF6 was degraded during CSFV infection or NS3 expression exclusively, indicating that CSFV and TRAF6 were mutually antagonistic and that TRAF6 degradation might contribute to persistent CSFV replication. Moreover, nuclear factor-kappa B (NF-κB) activity and interferon (IFN)-β and interleukin (IL)-6 expression were increased in TRAF6-overexpressing cells, whereas TRAF6-knockdown cells exhibited decreased NF-κB activity and IFN-β and IL-6 levels. Notably, TRAF6 overexpression did not reduce CSFV replication following inhibition of NF-κB activation by p65 knockdown. Our findings revealed that TRAF6 inhibits CSFV replication via activation of NF-κB-signalling pathways along with increases in the expression of its targets IFN-β and IL-6. This work addresses a novel aspect concerning the regulation of innate antiviral immune response during CSFV infection.
登录
查看更多内容
病毒感染诱导 USP25 通过介导 TRAF3 和 TRAF6 的稳定来促进先天抗病毒反应
DOI：
10.1073/pnas.1509968112
发表时间：
2015-09-08
影响因子：
11.1
作者：
Lin, Dandan;Zhang, Man;Zhong, Bo
通讯作者：
Zhong, Bo
影响因子：
3.7
作者：
TAMURA, JK;WARRENER, P;COLLETT, MS
通讯作者：
COLLETT, MS
影响因子：
5.4
作者：
Lamp, Benjamin;Riedel, Christiane;Ruemenapf, Till
通讯作者：
Ruemenapf, Till
影响因子：
4.4
作者：
Gohda, J;Matsumura, T;Inoue, J
通讯作者：
Inoue, J
影响因子：
10.5
作者：
Lomaga, MA;Yeh, WC;Mak, TW
通讯作者：
Mak, TW