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

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.

Automated summary

This study identifies the actin-regulating protein CAPG as an important factor in the replication of Ebola virus. Knockdown of CAPG specifically inhibits viral infectivity and yield of infectious particles. Mechanistic analysis reveals the requirement of CAPG for virus production from infected cells, and the interaction between CAPG and the viral protein VP40.