Desmocollin 2 is a dominant entry receptor for Epstein-Barr virus infection of epithelial cells

To identify host factors critical for EBV infection, we conducted a genome-wide CRISPR/Cas9 screening in HEK293-Cas9 cells, a cell line highly susceptible to EBV infection. HEK293-Cas9 cells stably transfected with CRISPR/Cas9 library GeCKO v2 (1000000049, Addgene) sgRNAs were incubated with EBfaV-GFP, and the GFP-negative cell populations were sorted, propagated and then re-infected with EBfaV-GFP to reconfirm the loss of susceptibility to EBV infection. Since the EBV-uninfected cells were potentially resistant to EBV infection due to gene knockout, genomic DNA from these cells was collected, and sgRNAs were sequenced, and analyzed using the MAGeCK algorithm. Two independent screenings were performed.