EPS8 Facilitates Uncoating of Influenza A Virus

Abstract

Summary: All viruses balance interactions between cellular machinery co-opted to support replication and host factors deployed to halt the infection. We use gene correlation analysis to perform an unbiased screen for host factors involved in influenza A virus (FLUAV) infection. Our screen identifies the cellular factor epidermal growth factor receptor pathway substrate 8 (EPS8) as the highest confidence pro-viral candidate. Knockout and overexpression of EPS8 confirm its importance in enhancing FLUAV infection and titers. Loss of EPS8 does not affect virion attachment, uptake, or fusion. Rather, our data show that EPS8 specifically functions during virion uncoating. EPS8 physically associates with incoming virion components, and subsequent nuclear import of released ribonucleoprotein complexes is significantly delayed in the absence of EPS8. Our study identifies EPS8 as a host factor important for uncoating, a crucial step of FLUAV infection during which the interface between the virus and host is still being discovered. : Gene correlation analysis identifies host factors with functional impacts on influenza A virus replication. The top pro-viral factor, EPS8, enhances viral gene expression and titers. Larson et al. identify the step during influenza A virus entry when EPS8 functions, establishing EPS8 as a co-factor for virion uncoating. Keywords: influenza virus, entry, uncoating, gene correlation analysis, NCI-60, epidermal growth factor receptor pathway substrate 8 (EPS8)