| http://purl.uniprot.org/citations/19376974 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19376974 | http://www.w3.org/2000/01/rdf-schema#comment | "Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism of cellular membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering RNA (siRNA) library that targets 140 host membrane-trafficking genes to identify genes required for both HCV subgenomic replication and infectious virus production. We identified 7 host cofactors of viral replication, including Cdc42 and Rock2 (actin polymerization), EEA1 and Rab5A (early endosomes), Rab7L1, and PI3-kinase C2gamma and PI4-kinase IIIalpha (phospholipid metabolism). Studies of drug inhibitors indicate actin polymerization and phospholipid kinase activity are required for HCV replication. We found extensive co-localization of the HCV replicase markers NS5A and double-stranded RNA with Rab5A and partial co-localization with Rab7L1. PI4K-IIIalpha co-localized with NS5A and double-stranded RNA in addition to being present in detergent-resistant membranes containing NS5A. In a comparison of type II and type III PI4-kinases, PI4Ks were not required for HCV entry, and only PI4K-IIIalpha was required for HCV replication. Although PI4K-IIIalpha siRNAs decreased HCV replication and virus production by almost 100%, they had no effect on initial HCV RNA translation, suggesting that PI4K-IIIalpha functions at a posttranslational stage. Electron microscopy identified the presence of membranous webs, which are thought to be the site of HCV replication, in HCV-infected cells. Pretreatment with PI4K-IIIalpha siRNAs greatly reduced the accumulation of these membranous web structures in HCV-infected cells. We propose that PI4K-IIIalpha plays an essential role in membrane alterations leading to the formation of HCV replication complexes."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0902693106"xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Randall G."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Yoon R."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Grakoui A."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Cooper J.D."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Mateu G."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Jordan T.X."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Heaton N.S."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Berger K.L."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/author | "Oakland T.E."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/pages | "7577-7582"xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/title | "Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication."xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://purl.uniprot.org/core/volume | "106"xsd:string |
| http://purl.uniprot.org/citations/19376974 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19376974 |
| http://purl.uniprot.org/citations/19376974 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19376974 |
| http://purl.uniprot.org/uniprot/P60953#attribution-BD2149986F08243C3321263F6B966C0A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19376974 |
| http://purl.uniprot.org/uniprot/Q15075#attribution-BD2149986F08243C3321263F6B966C0A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19376974 |
| http://purl.uniprot.org/uniprot/O75747#attribution-BD2149986F08243C3321263F6B966C0A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19376974 |
| http://purl.uniprot.org/uniprot/P42356#attribution-BD2149986F08243C3321263F6B966C0A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19376974 |
| http://purl.uniprot.org/uniprot/P20339#attribution-BD2149986F08243C3321263F6B966C0A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19376974 |
| http://purl.uniprot.org/uniprot/O14966#attribution-BD2149986F08243C3321263F6B966C0A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/19376974 |