Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line

Haizhen Zhu, Hongshan Zhao, Christin D. Collins, Sarah E. Eckenrode, Qingguo Run, Richard A McIndoe, James M. Crawford, David R. Nelson, Jin-Xiong She, Chen Liu

Research output: Contribution to journalArticle

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Abstract

Interferon alfa (IFN-α)-based treatment is the only therapeutic option for chronic hepatitis C viral infection. However, the molecular mechanisms of IFN-α antiviral activity are not completely understood. The recent development of an HCV replicon cell culture system provides a feasible experimental model to investigate the molecular details of IFN-induced direct antiviral activity in hepatocytes. In this report, we show that IFN-α can effectively inhibit HCV subgenomic RNA replication and suppress viral nonstructural protein synthesis. Using cDNA microarray analysis, we also show that the replicon cells have different gene expression profile compared with the parental hepatoma cells (Huh7). IFN-α can induce a number of responsive genes in the replicon cells. One of the genes, 6-16 (G1P3), can enhance IFN-α antiviral efficacy. In addition, we demonstrate that IFN-α can significantly activate STAT3 in hepatoma cells, suggesting that this pathway plays a role in IFN-α signaling. In conclusion, our results indicate that IFN-α antiviral activity is associated with activation of STAT3-signaling pathway and intracellular gene activation. Our results also suggest that IFN-α-induced target genes may play an important role in IFN-α anti-HCV activity.

Original languageEnglish (US)
Pages (from-to)1180-1188
Number of pages9
JournalHepatology
Volume37
Issue number5
DOIs
StatePublished - May 1 2003

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Replicon
Interferon-alpha
Antiviral Agents
Gene Expression
Cell Line
Hepatocellular Carcinoma
Viral Nonstructural Proteins
Genes
Chronic Hepatitis C
Virus Diseases
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Transcriptome
Transcriptional Activation
Hepatocytes
Theoretical Models
Cell Culture Techniques
RNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line. / Zhu, Haizhen; Zhao, Hongshan; Collins, Christin D.; Eckenrode, Sarah E.; Run, Qingguo; McIndoe, Richard A; Crawford, James M.; Nelson, David R.; She, Jin-Xiong; Liu, Chen.

In: Hepatology, Vol. 37, No. 5, 01.05.2003, p. 1180-1188.

Research output: Contribution to journalArticle

Zhu, H, Zhao, H, Collins, CD, Eckenrode, SE, Run, Q, McIndoe, RA, Crawford, JM, Nelson, DR, She, J-X & Liu, C 2003, 'Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line', Hepatology, vol. 37, no. 5, pp. 1180-1188. https://doi.org/10.1053/jhep.2003.50184
Zhu, Haizhen ; Zhao, Hongshan ; Collins, Christin D. ; Eckenrode, Sarah E. ; Run, Qingguo ; McIndoe, Richard A ; Crawford, James M. ; Nelson, David R. ; She, Jin-Xiong ; Liu, Chen. / Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line. In: Hepatology. 2003 ; Vol. 37, No. 5. pp. 1180-1188.
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