Foot-and-mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication
Foot-and-mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication
复制标题
口蹄疫病毒非结构蛋白 2B 与亲环蛋白 A 相互作用，调节病毒复制
DOI：
10.1096/fj.201701351
复制
发表时间：
2018-12-01
期刊：
影响因子：
4.8
通讯作者：
Zheng, Haixue
中科院分区：
文献类型：
--
作者：
Liu, Huisheng;Xue, Qiao;Zheng, Haixue
口蹄疫（FMD）是一种影响偶蹄动物的高度传染性病毒。为了更好地了解病原体FMD病毒（FMDV）的非结构蛋白2B在病毒复制过程中的作用，我们鉴定了一种与FMDV 2B相互作用的猪宿主蛋白亲环素A（CypA）。2B-CypA相互作用通过免疫共沉淀和GST pull-down试验证实。CypA在FMDV感染过程中具有抗病毒作用。CypA的过表达在蛋白水平上降低了FMDV前导蛋白（L-pro）和3A。CypA诱导的L-pro的还原促进了宿主蛋白质的合成，增强了宿主真核翻译起始因子（eIF）-4（eIF 4G）的完整性。L-pro和3A的还原依赖于蛋白酶体途径。CypA和L-pro或3A之间没有相互作用。然而，CypA诱导的L-pro和3A的减少被2B抑制，并且2B-CypA相互作用的破坏削弱了2B诱导的这种抑制作用。总之，我们的发现鉴定了CypA对FMDV的抗病毒作用，并提供了FMDV如何通过2B蛋白拮抗宿主抗病毒应答的关键见解。Xue，Q.，曹伟，杨，F.，马，L.，刘伟，张，K.，刘，X.，Zhu，Z.，郑惠南口蹄疫病毒非结构蛋白2B与亲环素A相互作用，调节病毒复制。
Foot-and-mouth disease (FMD) is a highly contagious virus that affects cloven-hoofed animals. To understand better the role of nonstructural protein 2B of the causative agent FMD virus (FMDV) in the process of virus replication, we identified a porcine host protein, cyclophilin A (CypA), which interacts with FMDV 2B. The 2B-CypA interaction was confirmed by coimmunoprecipitation and GST pull-down assays. CypA showed antiviral functions during FMDV infection. Overexpression of CypA decreased FMDV leader protein (L-pro) and 3A at protein levels. CypA-induced reduction of L-pro enhanced the synthesis of host proteins and increased the integrality of host eukaryotic translation initiation factor (eIF)-4 (eIF4G). The reduction of L-pro and 3A was dependent on the proteasome pathway. No interaction was identified between CypA and L-pro or 3A. However, CypA-induced reduction of L-pro and 3A was suppressed by 2B, and disruption of 2B-CypA interaction impaired this inhibitive effect induced by 2B. In summary, our findings identify the antiviral role of CypA against FMDV and provide key insights into how FMDV antagonizes host antiviral response by 2B protein.Liu, H., Xue, Q., Cao, W., Yang, F., Ma, L., Liu, W., Zhang, K., Liu, X., Zhu, Z., Zheng, H. Foot-and-mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication.