Using CRISPR screens to understand Flaviviridae pathogenesis

All human pathogenic viruses exploit host factors, and investigation is currently clarifying the host function that determines viral infection. CRISPR genetic screening strategy has successfully recognized host factors critical for entry, replication, and spread (14). After the Flaviviruses bind to the receptors of the host cell (23)and subsequent clathrin-mediated endocytosis, the viral genome is finally released to the cytosol (24-26). The viral RNA by 5'-cap structure binds to ribosomes, and a viral polyprotein is produced in the translation process that anchors to the ER membrane. The viral polyprotein cleavage by viral and cellular proteases results in structural and non-structural proteins (23, 27). Remarkably, other viral life cycle processes, such as viral RNA replication and virion assembly, occur at the ER. However, despite this awareness of these processes, there is little detailed understanding of the host proteins involved. According to the investigation performed so far, CRISPR screens indicated that flaviviruses require ER protein complexes. In addition, these screens have recognized some ER proteins needed for virus replication; In the following, we have discussed these factors thoroughly.