Abstract

BackgroundHepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed to eliminate virus completely from the patient's body.ResultsInterferon induced antiviral protein kinase R (PKR) has a role in the hepatitis C virus (HCV) treatment as dsRNA activated PKR has the capacity to phosphorylate the serine and threonine of E2 protein and dimerization viral RNA. E2 gene of hepatitis C virus (HCV) genotype 1 has an active role in IFN resistance. E2 protein inhibits and terminates the kinase activity of PKR by blocking it in protein synthesis and cell growth. This brings forward a possible relation of E2 and PKR through a mechanism via which HCV evades the antiviral effect of IFN.ConclusionA hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural anlysis has pointed out serine 75 and 277 of the HCV E2 gene as a promising candidate for the serine phosphorylation. It is proposed that serine phosphorylation of HCV E2 gene has a significant role in interferon resistance.

Highlights

  • Hepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan

  • To evaluate its function in disease succession, amplified envelope protein 2 (E2) gene was cloned in mammalian expression vector pc DNA 3.1

  • Documented sequences for 1a genotype from diversified areas of the world were compared with local envelope gene sequence to get the percentage nucleotide identity (PNI) (Table 1) and CLUSTAL W

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Summary

Introduction

Hepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan. Hepatitis C virus is a key universal health issue [1] affecting approximately 200 million individuals worldwide and over 4 million in the United States alone, where it is the most common blood-borne infection [2]. It is the main reason of persistent liver infection and the most familiar sign for liver transplantation [3]. HCV is a member of genus, hepacivirus, family Flaviviridae and is a positive sense single stranded RNA virus [6].

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