A CRISPR Activation Screen Identifies a Pan-avian Influenza Virus Inhibitory Host Factor

Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for viral infection. However, there has been no systematic screen to identify the host factors that when over-expressed are sufficient to prevent infection. In this study, we utilized CRISPR/dCas9 activation technology to perform a genome-wide overexpression screen to identify IAV restriction factors. The major hit from our screen, B4GALNT2, showed inhibitory activity against influenza viruses with an α2,3 linked sialic acid receptor preference. In fact, B4GALNT2 overexpression prevented the infection of every avian influenza virus strain tested, including the H5, H9, and H7 subtypes, which have previously caused disease in humans. Thus, we have utilized CRISPR/dCas9 activation technology to identify a factor that can completely abolish infection by avian influenza viruses.