title: Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones.
abstract: BACKGROUND
  Hepatitis C virus (HCV) RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system).
  
  
  RESULTS
  First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c) cells. In these latter, the HCV RNA has been eliminated by IFN-alpha treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB) Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-alpha-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis.
  
  
  CONCLUSIONS
  Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful for selection of antiviral targets.
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy. annarita.ciccaglione@iss.it
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Ciccaglione
authors.forename: Cinzia
authors.initials: C
authors.lastname: Marcantonio
authors.forename: Elena
authors.initials: E
authors.lastname: Tritarelli
authors.forename: Paola
authors.initials: P
authors.lastname: Tataseo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruni
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Germano
authors.initials: G
authors.lastname: Gerosolimo
authors.forename: Angela
authors.initials: A
authors.lastname: Costantino
authors.forename: Maria
authors.initials: M
authors.lastname: Rapicetta
mesh_terms: D045744:Cell Line, Tumor; D002999:Clone Cells; D016208:Databases, Factual; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005814:Genes, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D046228:Microarray Analysis; D008954:Models, Biological; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012093:Replicon / Q000235:genetics*; D015203:Reproducibility of Results; D014158:Transcription, Genetic; D014779:Virus Replication / Q000235:genetics
chemical_list: D012367:RNA, Viral