EPS8 facilitates uncoating of influenza A virus

Gloria P. Larson; Vy Tran; Shuiqìng Yú; Yíngyún Caì; Christina A. Higgins; Danielle M. Smith; Steven F. Baker; Sheli R. Radoshitzky; Jens H. Kuhn; Andrew Mehle

Step-wise investigation of the early stages of infection revealed that EPS8 functions independent of virion attachment, endosomal acidification, or HAdependent fusion. Rather, EPS8 specifically functioned during the uncoating of the incoming viral cores. Defects in viral uncoating slowed the kinetics of vRNP nuclear import in EPS8-edited cells, corresponding with the overall delay in viral gene expression and replication in these cells. These data . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. (Pinto et al., 1992) . The influx of potassium ions and protons into the virion interior initiates conformational changes that relax interactions between the matrix protein M1 and vRNPs, making the core competent for uncoating and disassembly of the RNP bundle (Stauffer et al., 2014) . Following fusion of the viral and host membranes, the core requires further processing to fully disassemble. Unanchored ubiquitin chains packaged within the virion help direct the core to the cellular aggresome where mechanical forces have been proposed to accelerate uncoating and release of vRNPs into the cytosol (Banerjee et al., 2014) . Our data now implicate EPS8 as another host factor important during these later stages of uncoating.