Virus Details


VHFID1907

Host Factor Information

Gene Name STT3B
HF Protein Name Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3B
HF Function Essential host factor of DENV
Uniprot ID Q8TCJ2
Protein Sequence View Fasta Sequence
NCBI Gene ID 201595
Host Factor (HF) Name in Paper STT3B
Gene synonyms SIMP
Ensemble Gene ID ENSG00000163527
Ensemble Transcript ENST00000295770
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0004579, GO:0005783, GO:0006516, GO:0006986, GO:0008250, GO:0016020, GO:0016021, GO:0018279, GO:0030433, GO:0043686, GO:0043687, GO:0046872,
MINT ID Q8TCJ2
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 608605
PANTHER ID N.A.
PDB ID(s) N.A.,
pfam ID PF02516,
Drug Bank ID N.A.,
ChEMBL ID N.A.
Organism Homo sapiens (Human)

Pathogen Information

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

Publication Information

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