title: An integrated transcriptomic and meta-analysis of hepatoma cells reveals factors that influence susceptibility to HCV infection.
abstract: Hepatitis C virus (HCV) is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc) systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies.
authors: Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Jamie I
authors: JI
authors: MacPherson
authors: Ben
authors: B
authors: Sidders
authors: Stefan
authors: S
authors: Wieland
authors: Jin
authors: J
authors: Zhong
authors: Paul
authors: P
authors: Targett-Adams
authors: Volker
authors: V
authors: Lohmann
authors: Perdita
authors: P
authors: Backes
authors: Oona
authors: O
authors: Delpuech-Adams
authors: Francis
authors: F
authors: Chisari
authors: Marilyn
authors: M
authors: Lewis
authors: Tanya
authors: T
authors: Parkinson
authors: David L
authors: DL
authors: Robertson
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D004198:Disease Susceptibility / Q000276:immunology / Q000473:pathology; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger