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

To overcome limitations of previous screening methodologies, we sought to identify both enhancers and suppressors of FLUAV replication in an unbiased manner. We utilized gene correlation analysis which relied on inherent differences in gene expression among different cell lines and consequently did not require external manipulation of the cellular environment. The National Cancer Institute-60 (NCI-60) panel consists of 59 distinct cell lines with well-characterized transcriptomic profiles (Shankavaram et al., 2007; Weinstein and Pommier, 2003) . The diversity of cell types and the depth of transcriptomic data permit high confidence genome-wide correlations between cellular gene expression and infection susceptibility (Kondratowicz et al., 2013; Lenaerts et al., 2012; Schowalter et al., 2012) . We therefore inoculated the NCI-60 panel of cell lines with a singlecycle variant of A/WSN/1933 (H1N1, WSN) encoding GFP (WSN-GFP) ( Figure 1A ). Using WSN-GFP, we specifically focused on host factors involved in early stages of infection up to and including viral gene expression and translation.