DDX56 cooperates with FMDV 3A to enhance FMDV replication by inhibiting the phosphorylation of IRF3
DDX56 cooperates with FMDV 3A to enhance FMDV replication by inhibiting the phosphorylation of IRF3
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DOI：
10.1016/j.cellsig.2019.109393
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发表时间：
2019-12-01
影响因子：
4.8
通讯作者：
Zheng, Hai-xue
中科院分区：
文献类型：
--
作者：
Fu, Shao-zu;Yang, Wen-ping;Zheng, Hai-xue
口蹄疫病毒(FMDV)的成分与宿主细胞蛋白相互作用，促进自身复制，逃避宿主免疫反应。以往的研究表明，口蹄疫病毒3A、2C和2B蛋白与参与口蹄疫病毒复制的宿主细胞蛋白相互作用。然而，其他宿主蛋白是否对口蹄疫病毒复制有影响尚不清楚。在本研究中，我们确定DDX56是口蹄疫病毒复制的正调控因子。DDX56过表达增加了口蹄疫病毒的复制，而DDX56基因敲除则有相反的作用。DDX56与口蹄疫病毒3A相互作用并协同作用，通过减少IRF3的磷酸化来抑制I型干扰素。此外，DDX56的D166位在促进口蹄疫病毒复制和与口蹄疫病毒3A协同抑制IRF3的磷酸化方面发挥了作用。此外，对DDX56或FMDV 3A的敲除结果也表明，DDX56与FMDV 3A协同抑制IRF3的磷酸化。这些结果表明，口蹄疫病毒3A蛋白与宿主蛋白DDX56之间的相互作用是口蹄疫病毒复制的关键。
The components of foot-and-mouth disease virus (FMDV) interact with host cellular proteins to promote self-replication and evade the host immune response. Previous studies have shown that FMDV 3A, 2C and 2B proteins interact with host cellular proteins involved in FMDV replication. However, whether the other host proteins have an impact on FMDV replication is less understood. In this study, we identified DDX56 as a positive regulator of FMDV replication. DDX56 overexpression increased FMDV replication, whereas DDX56 knockdown had the opposite effect. DDX56 interacted and cooperated with FMDV 3A to inhibit the type I interferon by reducing the phosphorylation of IRF3. Moreover, the D166 site of DDX56 played a role in increasing FMDV replication and cooperating with FMDV 3A to inhibit the phosphorylation of IRF3. Additionally, knockdown of DDX56 or FMDV 3A results also showed that DDX56 cooperated with FMDV 3A to inhibit the phosphorylation of IRF3. These results suggest that the interaction between FMDV 3A protein and the host protein DDX56 is critical for FMDV replication.