Classical swine fever virus NS4B protein interacts with MAVS and inhibits IL-8 expression in PAMs
Classical swine fever virus NS4B protein interacts with MAVS and inhibits IL-8 expression in PAMs
复制标题
猪瘟病毒 NS4B 蛋白与 MAVS 相互作用并抑制 PAM 中 IL-8 的表达
DOI：
10.1016/j.virusres.2021.198622
复制
发表时间：
2022
期刊：
影响因子：
5
通讯作者：
Huifang Lv
中科院分区：
文献类型：
--
作者：
Wang Dong;Huiyuan Jing;Wang Haihua;Cao Sufang;Yanting Sun;Zhang Yan;Huifang Lv
猪瘟病毒（classical swine fever virus，CSFV）是一种严重的猪传染病，给养猪业带来巨大的经济损失。猪瘟病毒NS 4 B蛋白对病毒复制和致病性至关重要。白细胞介素8（IL-8）是一种主要的趋化因子，由多种细胞诱导，在宿主防御多种病毒的机制中起重要作用。有报道称，猪瘟病毒NS 4A参与诱导猪脐静脉内皮细胞表达IL-8。然而，CSFV NS 4 B对IL-8表达的影响尚不清楚。在这项研究中，我们表明，猪瘟病毒NS 4 B抑制IL-8在猪肺泡巨噬细胞（PAM）的表达，和NS 4 B抑制线粒体抗病毒信号蛋白（MAVS）诱导的IL-8的表达。此外，CSFV NS 4 B与MAVS相互作用。然而，NS 4 B不改变MAVS表达。随后，我们证明了IRF 3敲低或NF-κB抑制降低了MAVS诱导的IL-8表达。此外，MAVS表达还激活了IRF 3和NF-κB通路。然而，CSFV NS 4 B抑制MAVS介导的NF-κB活化和IRF 3表达。最后，CSFV NS 4 B抑制IRF 3的表达。我们的研究结果表明，CSFV NS 4 B与MAVS相互作用，并通过阻断IRF 3和NF-κB的活化来抑制IL-8的表达。总之，这项研究提供了深入了解NS 4 B抑制IL-8表达的机制。
Classical swine fever virus (CSFV) infection causes a severe disease of pigs, resulting in significant economic losses. The CSFV NS4B protein is crucial for viral replication and pathogenicity. Interleukin 8 (IL-8), a main chemokine, is induced by multiple cell types and plays an essential role in host defense mechanisms against numerous viruses. It has been reported that NS4A of CSFV is involved in the induction of IL-8 expression in swine umbilical vein endothelial cells. However, the effect of CSFV NS4B on IL-8 expression is unknown. In this study, we showed that CSFV NS4B inhibited IL-8 expression in porcine alveolar macrophages (PAMs), and NS4B inhibited mitochondrial antiviral signaling protein (MAVS)-induced IL-8 expression. Moreover, CSFV NS4B interacted with MAVS. However, NS4B did not alter MAVS expression. Subsequently, we demonstrated that IRF3 knockdown or NF-κB inhibition reduced MAVS-induced IL-8 expression. Furthermore, the IRF3 and NF-κB pathways were activated by MAVS expression. However, CSFV NS4B inhibited MAVS-mediated NF-κB activation and IRF3 expression. Finally, CSFV NS4B inhibited IRF3 expression. Our findings reveal that CSFV NS4B interacts with MAVS and inhibits IL-8 expression by blocking the activation of IRF3 and NF-κB. Taken together, this study provides insights into the mechanism of NS4B-inhibited IL-8 expression.