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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Online
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1437-4331
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Volume 47, Issue 10

Issues

SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells

Marcello Persico / Roberta Russo / Eliana Persico / Monica Svelto / Daniela Spano / Immacolata Andolfo / Vincenzo La Mura / Mario Capasso / Claudio Tiribelli / Roberto Torella / Achille Iolascon
  • CEINGE Biotecnologie Avanzate, Napoli, Italy
  • Department of Biochemistry and Medical Biotechnologies, University Federico II of Naples, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar

Abstract

Background: The poor response to antiviral treatment of hepatitis C virus (HCV)-infected patients with genotype 1b has been associated with a higher prevalence of metabolic syndrome. However, the molecular link between these clinical entities is not clear. The goal of this study was to clarify the role of genotype 1b and 2 in the genetic expression of suppressor of cytokine signaling 3 (SOCS3) and insulin receptor substrate 1 (IRS-1).

Methods: We infected human hepatocellular carcinoma cell line (HepG2) cells with human HCV genotype 1b or 2 and measured the gene and protein expression of SOCS3 at various times. We also evaluated impairment in the insulin pathway by analysis of IRS-1 and phospho-AKT. For the control, we used HepG2 cell cultures treated with non-infectious serum. We also demonstrated the occurrence of HCV infection by the detection of both positive and negative strands in the cells and culture medium. To test infection of the HepG2 cells, we performed quantitative real-time polymerase chain reaction (qRT-PCR) of viral load at different time points. We analyzed the viral genotype in the pellet and supernatant.

Results: At each time point, we found positive and negative strands in the infected cells, while in the medium we found positive, but no negative strands. We also detected the presence of the correct genotype in the medium. Two weeks following infection when the viral load was higher, we tested genotype 1b and 2 infected cells. SOCS3 gene expression was significantly higher in genotype 1b-infected cells (median 2.56; mean 2.82±0.59) compared with genotype 2 (median 1.34; mean 1.46±0.31) (p=0.04) and control cells (median 1.09; mean 1.02±0.11, p=0.02). There was no difference between cells exposed to genotype 2 and control cells. Conversely, IRS-1 was significantly lower in genotype 1b-infected cells (median 15.97; mean 15.45±0.67) compared with genotype 2-infected cells (median 16.45; mean 16.44±0.01, p=0.04). Statistically significant differences were seen when comparing the pAKT/AKT ratio in genotype 1b-infected cells (0.19±0.034) and not genotype 1b-infected (genotype 2-infected and non-infected) cells (0.253±0.004, p=0.03). This inverse regulation is compatible with interactions between the molecular expression of SOCS3, IRS-1 and phospho-AKT mediated by the genotype 1b virus.

Conclusions: Up-regulation of the SOCS3 gene might be one of the mechanisms governing non-response to therapy and expression of insulin resistance mediated via a direct mechanism at this level of genotype 1b HCV.

Clin Chem Lab Med 2009;47:1217–25.

Keywords: hepatitis C virus; insulin receptor substrate 1 (IRS-1); suppressor of cytokine signaling 3 (SOCS3)

About the article

Corresponding author: Prof. Marcello Persico, MD, Internal Medicine and Hepatology Unit, Second University of Naples, Via Petrarca 101, 80100 Naples, Italy Phone: +390815666838, Fax: +390815666838,


Received: 2009-04-06

Accepted: 2009-06-29

Published in Print: 2009-10-01


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 47, Issue 10, Pages 1217–1225, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2009.280.

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