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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 and Achille Iolascon
Published/Copyright: October 1, 2009
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 47 Issue 10

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)
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: 2009-4-6
Accepted: 2009-6-29
Published Online: 2009-10-01
Published in Print: 2009-10-01

©2009 by Walter de Gruyter Berlin New York

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https://doi.org/10.1515/CCLM.2009.280
Keywords for this article
hepatitis C virus; insulin receptor substrate 1 (IRS-1); suppressor of cytokine signaling 3 (SOCS3)

Articles in the same Issue

  1. Editorial
  2. Cardiac troponins: what we knew, what we know – where are we now?
  3. Review
  4. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal?
  5. Opinion Papers
  6. A critical appraisal of experimental factors influencing the definition of the 99th percentile limit for cardiac troponins
  7. Genetic and biochemical heterogeneity of cardiac troponins: clinical and laboratory implications
  8. The future of hospital laboratories. Position statement from the Royal Belgian Society of Clinical Chemistry (RBSCC)
  9. Point
  10. Quantity quotient reporting. A proposal for a standardized presentation of laboratory results
  11. Counterpoint
  12. Quantity quotient reporting. Counterpoint
  13. Perspectives
  14. Increasing laboratory medicine activities in China: research and publications
  15. Contributions in Biochemistry and Molecular Biology from China and other top-ranking countries: a 10-year survey of the literature
  16. Genetics and Molecular Diagnostics
  17. SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells
  18. Polymorphisms of the β1-adrenergic receptor gene are associated with essential hypertension in Chinese
  19. Egyptian glycogen storage disease type III – identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId
  20. Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese
  21. –308G>A and –1031T>C tumor necrosis factor gene polymorphisms in Tunisian patients with coronary artery disease
  22. General Clinical Chemistry and Laboratory Medicine
  23. Error tracking in a clinical biochemistry laboratory
  24. HbA1c measurements from dried blood spots: validation and patient satisfaction
  25. Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection
  26. Cancer Diagnostics
  27. Detection of Meningeosis neoplastica by real-time quantitation of telomerase activity
  28. The prognostic utility of haptoglobin genotypes in squamous cell carcinoma of the head and neck
  29. Evaluation of a new method for the diagnosis of alterations of Lens culinaris agglutinin binding of thyroglobulin molecules in thyroid carcinoma
  30. The soluble transferrin receptor (TfR)-F-Index is not applicable as a test for iron status in patients with chronic lymphocytic leukemia
  31. Impact of calibration fitting models on the clinical value of chromogranin A
  32. Letters to the Editor
  33. Clinical value of a competitive NT-proBNP enzyme immunoassay compared to the Roche NT-proBNP platform
  34. Should gender-related reference values be used for total bilirubin?
  35. A novel nonsense mutation in the albumin gene (c.1275 C>A) causing analbuminemia in a Tunisian boy
  36. Abstracts
  37. 41st National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, 2nd Joint National Event SIBioC-SIMeL
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