Background
Understanding the cellular host factors that promote and inhibit viral
entry is important for identifying viral countermeasures. CRISPR whole
genome screens can be used to rapidly discover host factors that
contribute to or impair viral entry. However, when using the live
viruses and cellular lethality for selection, these screens can identify
an overwhelming number of genes without specificity for the stage of the
viral infection cycle. New screening methods are needed to identify host
machinery contributing to specific steps of viral infection. Here, we
developed a CRISPR whole genome screen and counter screen strategy based
on a pseudoviral platform that allowed identification of genes specific
to SARS-CoV-2 spike and vesicular stomatitis virus glycoprotein VSV-G
mediated entry.