Viruses 2019, 11(1), 68; https://doi.org/10.3390/v11010068
Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen
Viral Genomics and Vaccination Unit, UMR3569 CNRS, Virology department, Institut Pasteur, 75015 Paris, France
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Received: 14 December 2018 / Revised: 11 January 2019 / Accepted: 12 January 2019 / Published: 15 January 2019
(This article belongs to the Special Issue Emerging Viruses)
Abstract
Flaviviruses, such as dengue (DENV), West Nile (WNV), yellow fever (YFV) and Zika (ZIKV) viruses, are mosquito-borne pathogens that present a major risk to global public health. To identify host factors that promote flavivirus replication, we performed a genome-wide gain-of-function cDNA screen for human genes that enhance the replication of flavivirus reporter particles in human cells. The screen recovered seventeen potential host proteins that promote viral replication, including the previously known dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit (DDOST). Using silencing approaches, we validated the role of four candidates in YFV and WNV replication: ribosomal protein L19 (RPL19), ribosomal protein S3 (RPS3), DDOST and importin 9 (IPO9). Applying a panel of virological, biochemical and microscopic methods, we validated further the role of RPL19 and DDOST as host factors required for optimal replication of YFV, WNV and ZIKV. The genome-wide gain-of-function screen is thus a valid approach to advance our understanding of flavivirus replication. View Full-TextKeywords:
Flavivirus; West Nile virus; Yellow fever virus; Zika virus; Host-pathogen interactions; Virus replication; Genome-wide gain-of-function screen; Oligosaccharyltransferase complex; Ribosomal proteins
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Petrova, E.; Gracias, S.; Beauclair, G.; Tangy, F.; Jouvenet, N. Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen. Viruses 2019, 11, 68.
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