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

Given that both cell types exhibited similar phenotypes, we continued our investigation using the edited A549 cell lines, as these cells are of lung origin and more closely represent natural target cells during influenza virus infection. We assessed whether EPS8 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. Figure 2F ). Consistent with the results obtained using WSN, editing of EPS8 reduced viral gene expression for the influenza A strains S009 SRK PASTN and CA04 PASTN. Interestingly, EPS8 editing did not affect B/Brisbane PASTN gene expression ( Figure 2F ). We explored infection specificity further by assessing the relative infection rates of A549 cells overexpressing EPS8 in response to challenge by diverse viruses ( Figure S4 ). EPS8 expression levels did not alter infection rates of Marburg virus (MARV) or Junín virus (JUNV). In contrast, EPS8 overexpression caused decreased Ebola virus (EBOV), Venezuelan equine encephalitis virus (VEEV), and Rift Valley fever virus (RVFV) infection rates. Hence, altering EPS8 expression does not generically affect viral replication. Together, these data confirm that EPS8 acts as a pro-viral host factor during FLUAV infection and exhibits specific effects on cell infectivity depending on the virus.