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Open Access Highly Accessed Research

System-based proteomic analysis of the interferon response in human liver cells

Wei Yan1*, Hookeun Lee1, Eugene C Yi1, David Reiss1, Paul Shannon1, Bartlomiej K Kwieciszewski2, Carlos Coito2, Xiao-jun Li1, Andrew Keller1, Jimmy Eng1, Timothy Galitski1, David R Goodlett1, Ruedi Aebersold1 and Michael G Katze2

Author Affiliations

1 Institute for Systems Biology, Seattle, WA 98103, USA

2 Department of Microbiology and Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA

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Genome Biology 2004, 5:R54  doi:10.1186/gb-2004-5-8-r54

Published: 22 July 2004

Abstract

Background

Interferons (IFNs) play a critical role in the host antiviral defense and are an essential component of current therapies against hepatitis C virus (HCV), a major cause of liver disease worldwide. To examine liver-specific responses to IFN and begin to elucidate the mechanisms of IFN inhibition of virus replication, we performed a global quantitative proteomic analysis in a human hepatoma cell line (Huh7) in the presence and absence of IFN treatment using the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS/MS).

Results

In three subcellular fractions from the Huh7 cells treated with IFN (400 IU/ml, 16 h) or mock-treated, we identified more than 1,364 proteins at a threshold that corresponds to less than 5% false-positive error rate. Among these, 54 were induced by IFN and 24 were repressed by more than two-fold, respectively. These IFN-regulated proteins represented multiple cellular functions including antiviral defense, immune response, cell metabolism, signal transduction, cell growth and cellular organization. To analyze this proteomics dataset, we utilized several systems-biology data-mining tools, including Gene Ontology via the GoMiner program and the Cytoscape bioinformatics platform.

Conclusions

Integration of the quantitative proteomics with global protein interaction data using the Cytoscape platform led to the identification of several novel and liver-specific key regulatory components of the IFN response, which may be important in regulating the interplay between HCV, interferon and the host response to virus infection.