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Cell Rep. 2016 Jun 28;16(1):232-46. doi: 10.1016/j.celrep.2016.06.028. Epub 2016 Jun 21.

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

Author information

  • 1Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
  • 2Signaling Systems Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 3Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • 4Department 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.

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.

KEYWORDS:

AXL; CRISPR/Cas9 screen; EMC; MORR; RNAi screen; Zika virus; arbovirus; dengue virus; flavivirus; yellow fever virus

PMID:
27342126
DOI:
10.1016/j.celrep.2016.06.028
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