Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C.

Abstract

BACKGROUND:

Interferon (IFN)-α receptor 1 (ifnar1) and suppressor of cytokine signaling 1 (socs1) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2(⁻ΔΔCT)) with respect to hprt housekeeping gene was calculated.

RESULTS:

Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; P = 0.005). Ifnar1 transcription increased significantly (P = 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated.

CONCLUSION:

Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect ifnar1 and socs1 transcription, as well as in the ability to evade the antiviral response.

• Authors: Virginia Sedeño-Monge, Gerardo Santos-López, Rosa C Rocha-Gracia, Daniel Meléndez-Mena, Alberto Ramírez-Mata, Verónica Vallejo-Ruiz, Julio Reyes-Leyva
• Journal: Virology journal (Virol J) Vol. 7 Pg. 243 (Sep 18 2010) ISSN: 1743-422X [Electronic] England
• PMID: 20849643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• SOCS1 protein, human
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins
• Receptor, Interferon alpha-beta
• Ribavirin

Topics

• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Female
• Hepatitis C, Chronic (drug therapy, immunology, pathology)
• Humans
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Leukocytes, Mononuclear (immunology, virology)
• Male
• Middle Aged
• Receptor, Interferon alpha-beta (biosynthesis)
• Recombinant Proteins
• Ribavirin (therapeutic use)
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins (biosynthesis)
• Transcription, Genetic