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; Timothy F. Kowalik; Abraham L. Brass

doi:10.1016/j.celrep.2016.06.028

Cell Reports (Jun 2016)

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,
Timothy F. Kowalik,
Abraham L. Brass

Affiliations

George Savidis: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
William M. McDougall: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Paul Meraner: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Jill M. Perreira: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Jocelyn M. Portmann: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Gaia Trincucci: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Sinu P. John: Signaling Systems Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Aaron M. Aker: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Nicholas Renzette: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Douglas R. Robbins: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Zhiru Guo: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
Sharone Green: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
Timothy F. Kowalik: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA
Abraham L. Brass: Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA

DOI: https://doi.org/10.1016/j.celrep.2016.06.028
Journal volume & issue: Vol. 16, no. 1
pp. 232 – 246

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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