研究动态
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猪核仁蛋白NPM1基因在促进乙型脑炎病毒复制和炎症细胞因子诱导中的功能特性研究

Functional characterization of porcine nucleophosmin (NPM1) gene in promoting the replication of Japanese encephalitis virus and induction of inflammatory cytokines.

发表日期:2023 Aug 01
作者: Ying Liu, Linjie Zhang, Xuan Chen, Chuwen Sun, Yanbing Zhang, Yanhua Li, Chenxi Li
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

核磷酸酯酶 (NPM1) 是一种多功能核仁蛋白,参与细胞周期控制、肿瘤发生、炎症性细胞因子的诱导、病毒复制以及对各种应激刺激的细胞响应。然而,它在猪身上的生理功能并不清楚。在本研究中,我们克隆了猪NPM1(porNPM1)基因,并分析了porNPM1蛋白在猪身上的功能。完整的porNPM1基因编码了一个294个氨基酸的蛋白质,与哺乳动物中的同源物相比,其序列相似性为94.5% - 99.3%,并在各种猪组织中以mRNA水平广泛表达。porNPM1主要定位于ST细胞的细胞核中,而在紫外线照射或H2O2处理后从细胞核转位到核质溶胞。值得注意的是,日本脑炎病毒(JEV)感染阻止了porNPM1从核仁转位到核质溶胞。此外,porNPM1与JEV的C蛋白相互作用,并促进了在ST细胞中的JEV复制。porNPM1的过表达和敲除分别增强或损害了JEV的复制,表明porNPM1在JEV的复制中起着重要作用。此外,纯化的porNPM1的外区域诱导了炎症性细胞因子(TNF-α、IL-6和IL-8)的产生。综上,这些数据表明porNPM1参与了细胞的应激刺激、JEV的复制以及炎症性细胞因子的诱导。版权所有 © 2023. Elsevier Ltd. 发表。
Nucleophosmin (NPM1) is a multifunctional nucleolar protein that plays a role in cell cycle control, tumorigenesis, induction of the inflammatory cytokine, virus replication, as well as the cellular responses to a variety of stress stimuli. However, its physiological functions in pigs have not been well understood. Here, we cloned the porcine NPM1 (porNPM1) gene and analyzed the functions of the porNPM1 protein in pigs. The full-length porNPM1 gene encoded a 294-amino acid protein with 94.5%-99.3% sequence identity to its orthologues in mammals and was extensively expressed in various pig tissues at the mRNA level. The porNPM1 primarily localizes in the nucleus of ST cells, while it translocates from the nucleus to nucleoplasm upon UV irradiation or H2O2 treatment. Notably, JEV infection blocked the translocation of porNPM1 from the nucleolus to the nucleoplasm. Furthermore, porNPM1 interacted with the JEV C protein and facilitated JEV replication in ST cells. The overexpression and knockdown of porNPM1 respectively enhanced or impaired JEV replication, suggesting the important role of porNPM1 in JEV replication. Additionally, the purified ectodomain of porNPM1 induced the production of inflammatory cytokines (TNF-α, IL-6, and IL-8). Together, these data demonstrated that porNPM1 is involved in cellular stress stimuli, JEV replication, and induction of inflammatory cytokines.Copyright © 2023. Published by Elsevier Ltd.