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Open Access Highly Accessed Research article

Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

Anna Rita Ciccaglione1*, Cinzia Marcantonio1, Elena Tritarelli1, Paola Tataseo2, Alessandro Ferraris3, Roberto Bruni1, Bruno Dallapiccola3, Germano Gerosolimo2, Angela Costantino1 and Maria Rapicetta1

Author Affiliations

1 Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy

2 ASL Avezzano-Sulmona, Transfusional Medicine and Molecular Biology Laboratory, Sulmona, Italy

3 IRCCS CSS-Mendel Institute and Dept. of Experimental Medicine and Pathology, Sapienza University, Rome, Italy

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BMC Genomics 2008, 9:309  doi:10.1186/1471-2164-9-309

Published: 30 June 2008

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-α 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-α-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.

Conclusion

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.