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Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics
George Savidis1, William M McDougall1, Paul Meraner1
1Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
Cell Reports
|June 26, 2016
Summary
Dengue and Zika viruses rely on host cell machinery for infection. Researchers identified key host factors, including the endoplasmic reticulum membrane complex (EMC), essential for flavivirus replication.
Area of Science:
- Virology
- Molecular Biology
- Genomics
Background:
- Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses posing significant global health risks.
- Their geographic ranges are expanding, increasing the urgency to understand their replication mechanisms.
Purpose of the Study:
- To identify host cell factors essential for DENV and ZIKV infection.
- To elucidate the host-pathogen interactions governing flavivirus replication.
Main Methods:
- Orthologous functional genomic screens utilizing RNA interference (RNAi) and CRISPR/Cas9 technologies.
- Systematic identification of host genes impacting viral entry and replication.
Main Results:
- Screens identified AXL as a ZIKV entry factor.
- Key host factors involved in endocytosis, heparin sulfation, and protein processing were implicated.
- Both DENV and ZIKV were found to require the endoplasmic reticulum membrane complex (EMC) for early infection stages.
Conclusions:
- This study provides a comprehensive map of host-flavivirus interactions.
- The endoplasmic reticulum membrane complex (EMC) plays a critical role in the early replication cycle of DENV and ZIKV.
- Understanding these host dependencies offers potential targets for antiviral strategies.
