PCBP2促进口蹄疫病毒增殖的机制研究

doi:10.11843/j.issn.0366-6964.2018.07.014

摘要/Abstract

摘要：

多聚胞嘧啶结合蛋白2（PCBP2）是一个能特异性结合RNA和DNA Poly（C）片段的蛋白，具有维持mRNA稳定和调节翻译的功能；同时，PCBP2能负调控VISA介导的信号转导通路，抑制Ⅰ型干扰素（IFNs）的产生。前期研究表明，PCBP2能调节口蹄疫病毒（foot-and-mouth disease virus，FMDV）的增殖，但具体机制不清楚。作者对此进行了研究，发现：1）免疫共沉淀和GST pull-down试验证实，PCBP2能与FMDV结构蛋白VP0、VP2、2B、2C和3D相互作用；2）进一步用双荧光素酶报告系统试验证明，PCBP2负调控VISA介导的信号通路，并且2C、3D、VP0和2B促进PCBP2的负调控作用；3）通过Western blot试验表明，FMDV VP0蛋白能促进PCBP2对VISA的特异性降解。总之，PCBP2与FMDV VP0相互作用，促进PCBP2降解天然免疫接头蛋白VISA，抑制IFN-β的产生，从而有利于FMDV在细胞中的繁殖和生长。

关键词: 口蹄疫病毒, 天然免疫, 多聚胞嘧啶结合蛋白2, VISA, VP0

Abstract:

Poly(rC) binding protein 2(PCBP2) belongs to a class of proteins that bind to poly(C) stretches of both RNA and DNA. PCBP2 has roles in maintaining mRNA stability and regulating translation. Meanwhile PCBP2 is a negative regulator in VISA-mediated antiviral signaling to reduce production of IFN-β. Previous study have shown that PCBP2 can affect the multiplication of foot-and-mouth disease virus(FMDV), but the specific mechanism is unclear. Here, we investigated the molecular mechanisms about PCBP2 promoting the multiplication of FMDV. Results:1) We found that FMDV structural protein VP0, 2B, VP2, 2C and 3D can interact with PCBP2 via Co-IP and GST pull-down tests. 2) Further study revealed that PCBP2 is a negative regulator in VISA-mediated antiviral signaling, and 2C, 3D, VP0 and 2B can promote the negative regulation of PCBP2 on VISA-mediated antiviral signaling via the Dual-Luciferase Reporter Assay. 3) Meanwhile we found that FMDV VP0 can increase specific degradation of VISA mediated by PCBP2 through Western blot. In a word, FMDV VP0 can increase degradation of VISA mediated by PCBP2 via VP0-PCBP2 interaction to reduce the production of IFN-β, and enhance the FMDV activity in cell.

Key words: foot-and-mouth disease virus, innate immune, poly (rC) binding protein 2, mitochondrial antiviral signaling protein, VP0

中图分类号:

S852.659.6

何艳春, 杨文萍, 付绍祖, 郑海学, 杨孝朴. PCBP2促进口蹄疫病毒增殖的机制研究[J]. 畜牧兽医学报, 2018, 49(7): 1451-1459.

HE Yan-chun, YANG Wen-ping, FU Shao-zu, ZHENG Hai-xue, YANG Xiao-pu. The Research on Molecular Mechanism of PCBP2 Promoting the Multiplication of Foot-and-mouth Disease Virus[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(7): 1451-1459.

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