STANDARD_NAME KRISHNAN_FURIN_TARGETS_DN SYSTEMATIC_NAME M8701 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KRISHNAN_FURIN_TARGETS_DN NAMESPACE AFFY_Mouse430 DESCRIPTION_BRIEF Genes down-regulated in naive T lymphocytes lacking FURIN [GeneID=5045]: Cre-Lox knockout of FURIN in CD4+ [GeneID=920] cells. DESCRIPTION_FULL West Nile virus (WNV), and related flaviviruses such as tick-borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem. However, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited. WNV encodes only 10 proteins, implying that it may use many cellular proteins for infection. WNV enters the cytoplasm through pH-dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway. RNA interference (RNAi) presents a powerful forward genetics approach to dissect virus-host cell interactions. Here we report the identification of 305 host proteins that affect WNV infection, using a human-genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post-entry role for the endoplasmic-reticulum-associated degradation pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides a comprehensive molecular portrait of WNV-human cell interactions that forms a model for understanding single plus-stranded RNA virus infection, and reveals potential antiviral targets. PMID 18690214 GEOID AUTHORS Krishnan MN,Ng A,Sukumaran B,Gilfoy FD,Uchil PD,Sultana H,Brass AL,Adametz R,Tsui M,Qian F,Montgomery RR,Lev S,Mason PW,Koski RA,Elledge SJ,Xavier RJ,Agaisse H,Fikrig E CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Fig. 3bS FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1424359_at,1424518_at,1424838_at,1425875_a_at,1428020_at,1428197_at,1436275_at,1436686_at,1437307_at,1437713_x_at,1438340_at,1456172_at,1456914_at,1457166_at,1457548_at,1459291_at GENE_SYMBOLS OPLAH,,NCMAP,LEPR,RPF1,TSPAN9,KCNIP2,,SENP8,,ZNF385C,,,,,PTGR2 FOUNDER_NAMES