TY - JOUR
T1 - Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line
AU - Zhu, Haizhen
AU - Zhao, Hongshan
AU - Collins, Christin D.
AU - Eckenrode, Sarah E.
AU - Run, Qingguo
AU - McIndoe, Richard A.
AU - Crawford, James M.
AU - Nelson, David R.
AU - She, Jin Xiong
AU - Liu, Chen
N1 - Funding Information:
Abbreviations: HCV, hepatitis C virus; INF-α, interferon alfa; ISG, interferon-stimulated gene; PKR, double-strand RNA-dependent protein kinase; SDS, sodium dodecyl sulfate. From the 1Department of Pathology, Immunology, and Laboratory Medicine, and 2Department of Medicine, University of Florida College of Medicine, Gainesville, FL; and 3Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA. Received August 18, 2002; accepted February 16, 2003. Supported in part by HHMI start-up program Liver Scholar Award from the American Liver Foundation and NIDDK grant K08DK02958 (to C.L.), NIDDK biotech grant U24 DK58778 (to J.X.S.), and NIH grants DK2595 and HL64817 and GCRC grant RR00082 (to D.R.N.). Address reprint requests to: Chen Liu, M.D., Ph.D., Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610. E-mail: [email protected]; fax: 352-392-6249. Copyright © 2003 by the American Association for the Study of Liver Diseases. 0270-9139/03/3705-0028$30.00/0 doi:10.1053/jhep.2003.50184
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
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U2 - 10.1053/jhep.2003.50184
DO - 10.1053/jhep.2003.50184
M3 - Article
C2 - 12717400
AN - SCOPUS:0038185313
SN - 0270-9139
VL - 37
SP - 1180
EP - 1188
JO - Hepatology
JF - Hepatology
IS - 5
ER -