Classical swine fever virus NS5A protein changed inflammatory cytokine secretion in porcine alveolar macrophages by inhibiting the NF-κB signaling pathway.
Classical swine fever virus NS5A protein changed inflammatory cytokine secretion in porcine alveolar macrophages by inhibiting the NF-κB signaling pathway.
复制标题
经典的猪热病毒NS5A蛋白通过抑制NF-κB信号通路改变了猪肺泡巨噬细胞中炎症细胞因子的分泌。
DOI：
10.1186/s12985-016-0545-z
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发表时间：
2016-06-14
期刊：
影响因子：
4.8
通讯作者：
Tang SQ
中科院分区：
文献类型：
--
作者：
Dong XY;Tang SQ
猪瘟（Classical Swine Fever，CSF）是由猪瘟病毒（CSFV）引起的猪的一种高度接触性传染病。大量研究表明，CSFV非结构（NS）5A蛋白参与了CSFV的致病过程，但其作用机制尚不明确。本研究旨在探讨NS 5A蛋白在猪瘟病毒感染猪肺泡巨噬细胞（PAM）过程中的作用。体外培养的PAM经CSFV NS 5A转染后，ELISA检测IL-1β、IL-6和TNF-α表达的变化，Western blot和免疫荧光染色检测RIG-I信号通路活性与炎性细胞因子分泌的关系。结果表明，稳定表达的猪瘟病毒NS 5A蛋白对PAMs中炎性细胞因子IL-1β、IL-6和TNF-α的表达无明显影响，且NS 5A蛋白可抑制poly（I：C）诱导的PAMs中炎性细胞因子IL-1β、IL-6和TNF-α的表达。研究还表明，在没有poly（I：C）刺激的情况下，NS 5 A蛋白不会损害细胞中RIG-I、MDA 5、IPS-1、NF-κB和Ik B α的表达。在poly（I：C）刺激的细胞中，NS 5A蛋白对RIG-1、MDA 5、IPS-1、NF-κB蛋白表达无明显影响，而对poly（I：C）诱导的NF-κB核转位及活性有明显抑制作用。还观察到在表达NS 5A的细胞中poly（I：C）诱导的IkBα降解的抑制。这些结果表明，CSFV NS 5A蛋白通过抑制NF-κB信号通路，抑制poly（I：C）诱导的炎症细胞因子的分泌，可能参与了CSFV的致病过程。
Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of the pigs. A number of studies have suggested that CSFV non-structural (NS) 5A protein is involved in CSFV-associated pathogenesis, but its mechanism is still uncertain. The aim of this study was to investigate the roles of NS5A protein in CSFV-associated pathogenesis in cultured porcine alveolar macrophages (PAMs). After PAMs cultured in vitro were transfected with CSFV NS5A, the alterations in IL-1β, IL-6 and TNF-α expression were determined by ELISA, the RIG-I signaling activity related to inflammatory cytokine secretion was investigated by Western blot and Immunofluorescent staining. It was suggested that, the stable expressed CSFV NS5A solely had no influence on the expressions of inflammatory cytokines IL-1β, IL-6 and TNF-α in PAMs Moreover, NS5A protein could suppressed IL-1β, IL-6 and TNF-α expression induced by poly(I:C). It was also showed that NS5A protein did not impair the expressions of RIG-I, MDA5, IPS-1, NF-κB and IkBα in cells without poly(I:C) stimulation. Protein expressions of RIG-I, MDA5, IPS-1, NF-κB were not disrupted by NS5A protein in poly(I:C)-stimulated cells, while poly(I:C)-induced NF-κB nuclear translocation and activity was obviously suppressed by this protein. A suppression in poly(I:C)-induced IkBα degradation in NS5A-expressing cells was also observed. These data indicated that CSFV NS5A protein could inhibit the secretion of inflammatory cytokine induced by poly(I:C) through the suppression of the NF-κB signaling pathway, indicating the participation of CSFV NS5A protein in the pathogenesis of CSFV.