Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen.
Animals
Cell Line
Culicidae
/ virology
Dengue Virus
/ genetics
Flavivirus
/ genetics
Gene Library
Hexosyltransferases
/ genetics
Host-Pathogen Interactions
/ genetics
Humans
Karyopherins
/ genetics
Membrane Proteins
/ genetics
Ribosomal Proteins
/ genetics
Virus Replication
West Nile virus
/ genetics
Zika Virus
/ genetics
Flavivirus
Genome-wide gain-of-function screen
Host-pathogen interactions
Oligosaccharyltransferase complex
Ribosomal proteins
Virus replication
West Nile virus
Yellow fever virus
Zika virus
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
received:
14
12
2018
revised:
11
01
2019
accepted:
12
01
2019
entrez:
18
1
2019
pubmed:
18
1
2019
medline:
7
6
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30650657
pii: v11010068
doi: 10.3390/v11010068
pmc: PMC6356745
pii:
doi:
Substances chimiques
IPO9 protein, human
0
Karyopherins
0
Membrane Proteins
0
RPL19 protein, human
0
Ribosomal Proteins
0
ribosomal protein S3
0
Hexosyltransferases
EC 2.4.1.-
dolichyl-diphosphooligosaccharide - protein glycotransferase
EC 2.4.99.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Marie Curie International Reintegration program
ID : PCIG11-GA-2012-322060
Pays : International
Organisme : Agence Nationale de la Recherche
ID : ANR-12-JSV3-003-01
Pays : International
Organisme : Agence Nationale de la Recherche
ID : ANR-16-CE15-0025-01
Pays : International
Organisme : Ville de Paris EMERGENCE Program
ID : P766217
Pays : International
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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