Suppressor of cytokine signaling 1 expression in peripheral blood mononuclear cells of hepatitis C genotype 1 patients

Hepatitis C virus (HCV) is a global health problem, with an estimated prevalence of >185 million infections worldwide. About 399,000 people die every year because of HCV-associated liver complications such as liver cancer, liver cirrhosis, and hepatocellular carcinoma. Pakistan has the second-highest prevalence of HCV. The treatment of this life-threatening disease has always been a challenge, but the recent development of direct acting antivirals (DAAs) has offered hope to so many patients with this infection. Although DAAs have dramatically improved virologic clearance, their cost is prohibitive in low economic settings, which is why interferon (IFN) is still used in Pakistan and other developing countries. Many genes-specifically, interferon stimulating genes-alter treatment response. This study recruited 93 participants and used quantitative real-time polymerase chain reaction for the quantification of SOCS1 gene messenger RNA (mRNA) in the peripheral blood mononuclear cells of 5 different groups: IFN treated, IFN resistant, IFN nonresponders treated with DAAs, untreated, and healthy controls. A moderate positive correlation (r = 0.492) was observed between viral load and SOCS1 mRNA expression level. Our results suggest the over-expression of SOCS1 in PBMCs of IFN non-responders as compared to responders and DAA treated IFN non-responders.

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An Increase in Expression of SOCS1 Gene with Increase in Hepatitis C Virus Viral Load

Wahid

Rafique

Saleem

et al. 2018

Journal of Interferon & Cytokine Research

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Expression of SOCS1 and SOCS3 Genes in Interferon-Treated and Direct-Acting Antiviral Drugs-Treated Hepatitis C Patients

Naz

Wahid

Usman

et al. 2018

Journal of Interferon & Cytokine Research

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Genetics of host plays a significant role in susceptibility and pathogenesis of disease. During hepatitis C virus (HCV) infection, HCV proteins interfere with interferon (IFN) signaling pathways and upregulate transcription of suppressor of cytokine signaling 1 and 3 genes (SOCS1 and SOCS3), which results in impaired immune response. In this study, we evaluated relative expression of SOCS1 and SOCS3 in untreated HCV patients and patients treated with 2 different treatment strategies that are, (IFN therapy and direct-acting antiviral (DAA) drug regimen. To study gene expression, peripheral blood mononuclear cells (PBMCs) were isolated by using Histopaque. Total RNA was extracted from PBMCs by using BIOzol. Nine microgram of total RNA from each sample was used and reverse transcribed into single-stranded complementary DNA (cDNA) by using M-MLV reverse transcriptase (Invitrogen). The synthesized cDNA was diluted to a final concentration of 500 ng/μL. This diluted cDNA was further used for expression analysis of SOCS1and SOCS3 genes using Rotor Gene Q Real-Time PCR Detection System (QIAGEN). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was amplified as a housekeeping gene. We found that the SOCS1 expression in IFN and DAA-treated patient groups was 5.4 fold and 1.2 fold, respectively, high compared with the healthy controls (IFN versus healthy, P = 0.019 and DAA versus healthy, P = 0.91), whereas the SOCS3 expression in IFN and DAA-treated patient groups was 3.7 fold and 2 fold, respectively, high in comparison with the expression in healthy controls (IFN versus healthy, P = 0.025 and DAA versus healthy, P = 0.03). We also found a significant difference in the relative expression of SOCS1 and SOCS3 in DAAs-treated and IFN/ribavirin (RBV)-treated and untreated individual. We concluded that by targeting HCV proteins with DAAs, SOCS1, and SOCS3 transcription can be more effectively normalized compared to the treatment with IFN/RBV therapy.

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Role of SOCS1 Gene in Chronic Hepatitis C Virus Patients: A Mini-Review

Wahid

2020

Journal of Interferon & Cytokine Research

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Suppressor of cytokine signaling 1 expression in peripheral blood mononuclear cells of hepatitis C genotype 1 patients

Abstract: Peripheral blood SOCS1 expression before treatment was not associated with SVR in HCV genotype 1 patients treated with pegylated IFN-α and ribavirin.

Cited by 4 publications

References 32 publications

An Increase in Expression of SOCS1 Gene with Increase in Hepatitis C Virus Viral Load

An Increase in Expression of SOCS1 Gene with Increase in Hepatitis C Virus Viral Load

Expression of SOCS1 and SOCS3 Genes in Interferon-Treated and Direct-Acting Antiviral Drugs-Treated Hepatitis C Patients

Role of SOCS1 Gene in Chronic Hepatitis C Virus Patients: A Mini-Review

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