CAPG 对于控制感染细胞中病毒的出芽从而在埃博拉病毒感染中是必需的。

CAPG Is Required for Ebola Virus Infection by Controlling Virus Egress from Infected Cells.

机构信息

Department of Microbiology, NEIDL, Boston University School of Medicine, Boston, MA 02215, USA.

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.

出版信息

Viruses. 2022 Aug 28;14(9):1903. doi: 10.3390/v14091903.

DOI:10.3390/v14091903

PMID:36146710

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9505868/

Abstract

The replication of Ebola virus (EBOV) is dependent upon actin functionality, especially at cell entry through macropinocytosis and at release of virus from cells. Previously, major actin-regulatory factors involved in actin nucleation, such as Rac1 and Arp2/3, were shown important in both steps. However, downstream of nucleation, many other cell factors are needed to control actin dynamics. How these regulate EBOV infection remains largely unclear. Here, we identified the actin-regulating protein, CAPG, as important for EBOV replication. Notably, knockdown of CAPG specifically inhibited viral infectivity and yield of infectious particles. Cell-based mechanistic analysis revealed a requirement of CAPG for virus production from infected cells. Proximity ligation and split-green fluorescent protein reconstitution assays revealed strong association of CAPG with VP40 that was mediated through the S1 domain of CAPG. Overall, CAPG is a novel host factor regulating EBOV infection through connecting actin filament stabilization to viral egress from cells.

摘要

埃博拉病毒（EBOV）的复制依赖于肌动蛋白的功能，特别是在通过巨胞饮作用进入细胞和从细胞中释放病毒时。先前，涉及肌动蛋白成核的主要肌动蛋白调节因子，如 Rac1 和 Arp2/3，在这两个步骤中都很重要。然而，成核之后，需要许多其他细胞因子来控制肌动蛋白动力学。这些因子如何调节 EBOV 感染在很大程度上仍不清楚。在这里，我们确定了肌动蛋白调节蛋白 CAPG 对 EBOV 复制很重要。值得注意的是，CAPG 的敲低特异性地抑制了病毒的感染性和感染性颗粒的产量。基于细胞的机制分析显示，CAPG 是从感染细胞中产生病毒所必需的。邻近连接和分裂绿色荧光蛋白重建测定显示，CAPG 与 VP40 强烈相关，这种关联是通过 CAPG 的 S1 结构域介导的。总的来说，CAPG 是一种通过将肌动蛋白丝稳定与病毒从细胞中逸出联系起来调节 EBOV 感染的新型宿主因子。