| Gene Name | OST4 |
| HF Protein Name | Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 4 |
| HF Function | Essential host factor of DENV |
| Uniprot ID | P0C6T2 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 100128731 |
| Host Factor (HF) Name in Paper | OST4 |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000228474 |
| Ensemble Transcript | ENST00000429985;ENST00000447619;ENST00000456793 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0008250, GO:0016021, GO:0018279, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | N.A. |
| PANTHER ID | N.A. |
| PDB ID(s) | 2LAT, |
| pfam ID | PF10215, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Dengue virus 2 |
| Virus Short Name | DENV 2 |
| Order | Unassigned |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Dengue virus |
| Host | Human, mammals, mosquitoes and ticks |
| Cell Tropism | Phagocytes, hepatocytes |
| Associated Disease | Dengue fever |
| Mode of Transmission | Arthropod bite, mainly mosquitoes |
| VIPR DB link | http://www.viprbrc.org/brc/home.spg?decorator=flavi |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/flaviviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Flaviviridae |
| Paper Title | Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens |
| Author's Name | Caleb D. Marceau, Andreas S. Puschnik, Karim Majzoub, Yaw Shin Ooi, Susan M. Brewer, Gabriele Fuchs, Kavya Swaminathan, Miguel A. Mata, Joshua E. Elias, Peter Sarnow & Jan E. Carette |
| Journal Name | NATURE |
| Pubmed ID | 27383987 |
| Abstract | The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide1. No approved antivirals are available to date, and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates2. Hepatitis C virus (HCV) also remains a major medical problem, with 160 million chronically infected patients worldwide and only expensive treatments available3. Despite distinct differences in their pathogenesis and modes of transmission, the two viruses share common replication strategies4. A detailed understanding of the host functions that determine viral infection is lacking. Here we use a pooled CRISPR genetic screening strategy5,6 to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified endoplasmic-reticulum (ER)-associated multi-protein complexes involved in signal sequence recognition, N-linked glycosylation and ER-associated degradation. DENV replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as the crucial step requiring the OST complex. Moreover, we show that viral non-structural proteins bind to the OST complex. The identified ER-associated protein complexes were also important for infection by other mosquito-borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects7. By contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA-binding proteins and enzymes involved in metabolism. We found an unexpected link between intracellular flavin adenine dinucleotide (FAD) levels and HCV replication. This study shows notable divergence in host- dependencyfactorsbetweenDENVandHCV,andilluminatesnew host targets for antiviral therapy. |
| Used Model | HAP1 and Huh7.5.1 cells |
| DOI | 10.1038/nature18631 |
