Liu Huisheng, Xue Qiao, Cao Weijun, Yang Fan, Ma Linna, Liu Wenjie, Zhang Keshan, Liu Xiangtao, Zhu Zixiang, Zheng Haixue
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
FASEB J. 2018 Jun 15:fj201701351. doi: 10.1096/fj.201701351.
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) and 3A at protein levels. CypA-induced reduction of L enhanced the synthesis of host proteins and increased the integrality of host eukaryotic translation initiation factor (eIF)-4γ (eIF4G). The reduction of L and 3A was dependent on the proteasome pathway. No interaction was identified between CypA and L or 3A. However, CypA-induced reduction of L 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.
口蹄疫（FMD）是一种影响偶蹄类动物的高度传染性病毒。为了更好地了解口蹄疫病毒（FMDV）病原体的非结构蛋白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）。通过免疫共沉淀和GST下拉实验证实了2B与CypA的相互作用。在FMDV感染期间，CypA表现出抗病毒功能。CypA的过表达在蛋白水平上降低了FMDV前导蛋白（L）和3A。CypA诱导的L蛋白减少增强了宿主蛋白的合成，并增加了宿主真核翻译起始因子（eIF）-4γ（eIF4G）的完整性。L蛋白和3A的减少依赖于蛋白酶体途径。未发现CypA与L或3A之间存在相互作用。然而，2B抑制了CypA诱导的L蛋白和3A的减少，并且破坏2B-CypA相互作用削弱了2B诱导的这种抑制作用。总之，我们的研究结果确定了CypA对FMDV的抗病毒作用，并为FMDV如何通过2B蛋白拮抗宿主抗病毒反应提供了关键见解。-刘，H.，薛，Q.，曹，W.，杨，F.，马，L.，刘，W.，张，K.，刘，X.，朱，Z.，郑，H. 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
