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神经坏死病毒感染时,来自斜带石斑鱼的蛋白酶体亚基β型-8 通过干扰 NF-κB 信号通路来负调控细胞因子反应。

Proteasome subunit beta type-8 from sevenband grouper negatively regulates cytokine responses by interfering NF-κB signaling upon nervous necrosis viral infection.

机构信息

Department of Aqualife Medicine, Chonnam National University, Yeosu, Republic of Korea.

Institute of Marine Biotechnology, Pukyong National University, Busan, Republic of Korea.

出版信息

Fish Shellfish Immunol. 2021 Jun;113:118-124. doi: 10.1016/j.fsi.2021.04.004. Epub 2021 Apr 13.

Abstract

During viral infection, proper regulation of immune signaling is essential to ensure successful clearance of virus. Immunoproteasome is constitutively expressed and gets induced during viral infection by interferon signaling and contributes to regulate proinflammatory cytokine production and activation of the NF-κB pathway. In this study, we identified Hs-PSMB8, a member of the proteasome β-subunits (PSMB) family, as a negative regulator of NF-κB responses during NNV infection. The transient expression of Hs-PSMB8 delayed the appearance of cytopathic effect (CPE) and showed a higher viral load. The Hs-PSMB8 interacted with NNV which was confirmed using immunocolocalization and co-IP. Overexpression of Hs-PSMB8 diminished virus induced activation of the NF-κB promoters and downregulated the activation of IL-1β, TNFα, IL6, IL8, IFNγ expression upon NNV infection. Collectively, our results demonstrate that PSMB8 is an important regulator of NF-κB signaling during NNV infection in sevenband grouper.

摘要

在病毒感染期间,适当调节免疫信号对于确保成功清除病毒至关重要。免疫蛋白酶体在干扰素信号的作用下持续表达,并在病毒感染时被诱导,有助于调节促炎细胞因子的产生和 NF-κB 途径的激活。在本研究中,我们鉴定出 Hs-PSMB8,一种蛋白酶体 β 亚基(PSMB)家族的成员,是在 NNV 感染期间 NF-κB 反应的负调控因子。Hs-PSMB8 的瞬时表达延迟了细胞病变效应(CPE)的出现,并显示出更高的病毒载量。通过免疫共定位和共免疫沉淀证实了 Hs-PSMB8 与 NNV 的相互作用。Hs-PSMB8 的过表达降低了病毒诱导的 NF-κB 启动子的激活,并下调了 NNV 感染时 IL-1β、TNFα、IL6、IL8 和 IFNγ 的表达。总之,我们的研究结果表明,PSMB8 是七带石斑鱼中 NNV 感染期间 NF-κB 信号的重要调节因子。

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