Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/11/1/68 |
| _version_ | 1818194676241399808 |
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| author | Evgeniya Petrova Ségolène Gracias Guillaume Beauclair Frédéric Tangy Nolwenn Jouvenet |
| author_facet | Evgeniya Petrova Ségolène Gracias Guillaume Beauclair Frédéric Tangy Nolwenn Jouvenet |
| author_sort | Evgeniya Petrova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T01:06:04Z |
| format | Article |
| id | doaj.art-dce8601e38274394a2e3d75c912986b8 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-12T01:06:04Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-dce8601e38274394a2e3d75c912986b82022-12-22T00:43:35ZengMDPI AGViruses1999-49152019-01-011116810.3390/v11010068v11010068Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function ScreenEvgeniya Petrova0Ségolène Gracias1Guillaume Beauclair2Frédéric Tangy3Nolwenn Jouvenet4Viral Genomics and Vaccination Unit, UMR3569 CNRS, Virology department, Institut Pasteur, 75015 Paris, FranceViral Genomics and Vaccination Unit, UMR3569 CNRS, Virology department, Institut Pasteur, 75015 Paris, FranceViral Genomics and Vaccination Unit, UMR3569 CNRS, Virology department, Institut Pasteur, 75015 Paris, FranceViral Genomics and Vaccination Unit, UMR3569 CNRS, Virology department, Institut Pasteur, 75015 Paris, FranceViral Genomics and Vaccination Unit, UMR3569 CNRS, Virology department, Institut Pasteur, 75015 Paris, FranceFlaviviruses, 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.http://www.mdpi.com/1999-4915/11/1/68FlavivirusWest Nile virusYellow fever virusZika virusHost-pathogen interactionsVirus replicationGenome-wide gain-of-function screenOligosaccharyltransferase complexRibosomal proteins |
| spellingShingle | Evgeniya Petrova Ségolène Gracias Guillaume Beauclair Frédéric Tangy Nolwenn Jouvenet Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen Viruses Flavivirus West Nile virus Yellow fever virus Zika virus Host-pathogen interactions Virus replication Genome-wide gain-of-function screen Oligosaccharyltransferase complex Ribosomal proteins |
| title | Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen |
| title_full | Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen |
| title_fullStr | Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen |
| title_full_unstemmed | Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen |
| title_short | Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen |
| title_sort | uncovering flavivirus host dependency factors through a genome wide gain of function screen |
| topic | Flavivirus West Nile virus Yellow fever virus Zika virus Host-pathogen interactions Virus replication Genome-wide gain-of-function screen Oligosaccharyltransferase complex Ribosomal proteins |
| url | http://www.mdpi.com/1999-4915/11/1/68 |
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