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Type: Journal article
Title: Differential Expression of the CXCR3 Ligands in Chronic Hepatitis C Virus (HCV) Infection and Their Modulation by HCV In Vitro
Author: Helbig, K.
Ruszkiewicz, A.
Lanford, R.
Berzsenyi, M.
Harley, H.
McColl, S.
Beard, M.
Citation: Journal of Virology, 2009; 83(2):836-846
Publisher: Amer Soc Microbiology
Issue Date: 2009
ISSN: 0022-538X
Statement of
Karla J. Helbig, Andrew Ruszkiewicz, Robert E. Lanford, Mark D. Berzsenyi, Hugh A. Harley, Shaun R. McColl, and Michael R. Beard
Abstract: To investigate chemokine expression networks in chronic hepatitis C virus (HCV) infection, we used microarray analysis to determine chemokine expression in human infection and in chimpanzees experimentally infected with HCV. The CXCR3 chemokine family was highly expressed in both human and chimpanzee infection. CXCL10 was the only CXCR3 chemokine elevated in the serum, suggesting that it may neutralize any CXCR3 chemokine gradient established between the periphery and liver by CXCL11 and CXCL9. Thus, CXCR3 chemokines may not be responsible for recruitment of T lymphocytes but may play a role in positioning these cells within the liver. The importance of the CXCR3 chemokines, in particular CXCL11, was highlighted by replicating HCV (JFH-1) to selectively upregulate its expression in response to gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). This selective upregulation was confirmed at the transcriptional level by using the CXCL11 promoter driving the luciferase reporter gene. This synergistic increase in expression was not a result of HCV protein expression but the nonspecific innate response to double-stranded RNA (dsRNA), as both in vitro-transcribed HCV RNA and the dsRNA analogue poly(I:C) increased CXCL11 expression and promoter activity. Furthermore, we show that CXCL11 is an IRF3 (interferon regulatory factor 3) response gene whose expression is selectively enhanced by IFN-gamma and TNF-alpha. In conclusion, the CXCR3 chemokines are the most significantly expressed chemokines in chronic hepatitis C and most likely play a role in positioning T cells in the liver. Furthermore, HCV can selectively increase CXCL11 expression in response to IFN-gamma and TNF-alpha stimulation that may play a role in the pathogenesis of HCV-related liver disease.
Keywords: Liver
Cells, Cultured
Pan troglodytes
Hepatitis C, Chronic
Tumor Necrosis Factor-alpha
Oligonucleotide Array Sequence Analysis
Gene Expression Profiling
Genes, Reporter
Chemokine CXCL10
Chemokine CXCL9
Chemokine CXCL11
DOI: 10.1128/JVI.01388-08
Published version:
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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