Cellular cofactors affecting hepatitis C virus infection and replication

• DOI: 10.1073/pnas.0704894104
• Publication Date: 2007-07-07T00:41:41Z
• Authors: Glenn Randall; Maryline Panis; Jacob D. Cooper; Timothy L. Tellin...; Karen E. Sukhodolets; Sebastien Pfeffer; Markus Landthaler; Pablo Landgraf; Sherry Kan; Brett D. Lindenbach; Minchen Chien; David B. Weir; James J. Russo; Jingyue Ju; Michael J. Browns...; Robert Sheridan; Chris Sander; Mihaela Zavolan; Thomas Tuschl; Charles M. Rice
• Keywords: Dicer; NS5A; Replicon; NS2-3 protease; Host factors

Recently identified hepatitis C virus (HCV) isolates that are infectious in cell culture provide a genetic system to evaluate the significance of virus-host interactions for HCV replication. We have completed systematic RNAi screen wherein siRNAs were designed target 62 host genes encoding proteins physically interact with RNA or belong cellular pathways thought modulate infection. This includes 10 we identify this study bind NS5A. 26 these alter production >3-fold. Included set Dicer, principal component silencing pathway. Contrary hypothesis is an antiviral pathway mammals, as has been reported subgenomic replicons, Dicer inhibited Furthermore, several other components also inhibit MicroRNA profiling human liver, hepatoma Huh-7.5 cells, and cells harbor replicating demonstrated miR-122 predominant microRNA each environment. previously implicated positively regulating replication genotype 1 replicons. find 2'-O-methyl antisense oligonucleotide depletion inhibits 2a production. Our data define infection indicate requirement functional dominant over any activity may exert against HCV.