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

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.

• Authors: Wei Yan, Hookeun Lee, Eugene C Yi, David Reiss, Paul Shannon, Bartlomiej K Kwieciszewski, Carlos Coito, Xiao-jun Li, Andrew Keller, Jimmy Eng, Timothy Galitski, David R Goodlett, Ruedi Aebersold, Michael G Katze
• Journal: Genome biology (Genome Biol) Vol. 5 Issue 8 Pg. R54 ( 2004) ISSN: 1474-760X [Electronic] England
• PMID: 15287976 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proteome
• Interferons

Topics

• Cell Line, Tumor
• Computational Biology
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Hepatocytes (drug effects, immunology, metabolism, virology)
• Humans
• Interferons (pharmacology)
• Mass Spectrometry
• Protein Binding
• Proteome (genetics, metabolism)
• Proteomics
• Signal Transduction (drug effects)
• Software
• Substrate Specificity
• Systems Biology
• Viruses (immunology)