Reid St Patrick, Shurtleff Amy C, Costantino Julie A, Tritsch Sarah R, Retterer Cary, Spurgers Kevin B, Bavari Sina
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
Antiviral Res. 2014 Sep;109:171-4. doi: 10.1016/j.antiviral.2014.07.004. Epub 2014 Jul 11.
Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures.
迫切需要开发针对高致病性埃博拉病毒的新策略。一项蛋白质组学研究确定内质网伴侣蛋白HSPA5是一种与埃博拉病毒相关的宿主蛋白。在此,我们使用HSPA5抑制剂(-)-表没食子儿茶素没食子酸酯(EGCG)表明,该伴侣蛋白对病毒感染至关重要,从而证明了这种关联的功能意义。此外,体外和体内基因靶向均损害了病毒复制,并在致死性感染模型中保护了动物。这些发现表明,HSPA5对病毒复制至关重要,可作为设计基于宿主的对策的可行靶点。