title: Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics.
abstract: The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of 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, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: George
authors.initials: G
authors.lastname: Savidis
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: McDougall
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Meraner
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Perreira
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Portmann
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Gaia
authors.initials: G
authors.lastname: Trincucci
authors.affiliation: Signaling Systems Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sinu P
authors.initials: SP
authors.lastname: John
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Aker
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Renzette
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Robbins
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Zhiru
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Kowalik
authors.affiliation: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA; Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: abraham.brass@umassmed.edu.
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Brass
mesh_terms: D064113:CRISPR-Cas Systems; D002462:Cell Membrane / Q000378:metabolism; D003716:Dengue Virus / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005820:Genetic Testing; D023281:Genomics / Q000379:methods*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D034622:RNA Interference; D014779:Virus Replication; D000071244:Zika Virus / Q000235:genetics*
keywords: AXL; CRISPR/Cas9 screen; EMC; MORR; RNAi screen; Zika virus; arbovirus; dengue virus; flavivirus; yellow fever virus