Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

Usman A Ashfaq,Muhammad Tariq Awan,Muhammad Qasim,Muhammad Z Yousaf,Shah Jahan

doi:10.1186/1479-5876-9-194

Abstract

BackgroundHCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV.Methods and resultThe present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells.ConclusionOur data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.

Highlights

Hepatitis C virus (HCV) causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death
Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCV pseudoparticles (HCVpp) entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer
HCV infection is mainly restricted to hepatocytes, and since most of the infected individuals fail to spontaneously clear the virus from the liver, this leads to a chronic infection that can evolve towards liver fibrosis, cirrhosis and hepatocellular carcinoma over a period of decades [2]

Summary

Introduction

HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. HCV infection is mainly restricted to hepatocytes, and since most of the infected individuals fail to spontaneously clear the virus from the liver, this leads to a chronic infection that can evolve towards liver fibrosis, cirrhosis and hepatocellular carcinoma over a period of decades [2]. HCV is a small enveloped virus with a positive-sense, single-stranded RNA genome that encodes a large polyprotein of 3010 amino acids. HCV envelop protein E1 and E2 are highly glycosylated and play an important role in cell entry.

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Conclusion