Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics

George Savidis, William M. McDougall, Paul Meraner, Jill M. Perreira, Jocelyn M. Portmann, Gaia Trincucci, Sinu P. John, Aaron M. Aker, Nicholas Renzette, Douglas R. Robbins, Zhiru Guo, Sharone Green (+2 others)
2016 Cell Reports  
Graphical Abstract Highlights d RNAi and CRISPR/Cas9 screens were used to find flavivirus dependencies d The screens recovered host factors involved in endocytosis and heparin sulfation d The EMC is required by DENV and ZIKV in the early stages of replication d These studies give a systems-wide view of human-flavivirus interactions SUMMARY The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of
more » ... DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/ Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systemswide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
doi:10.1016/j.celrep.2016.06.028 pmid:27342126 fatcat:kzcyze5irfditcbcvd7awi6aqy