title: Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for hepatitis C virus replication.
abstract: Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern, Medical Center, Dallas, Texas, USA.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Chen
authors.forename: Bray
authors.initials: B
authors.lastname: Denard
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
mesh_terms: D002460:Cell Line; D044127:Epigenesis, Genetic; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D064547:Myxovirus Resistance Proteins; D014779:Virus Replication
chemical_list: D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins