Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies
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RESEARCH
Open Access
Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies Usman A Ashfaq1*, Muhammad Qasim1, Muhammad Z Yousaf2, Muhammad Tariq Awan1 and Shah Jahan3
Abstract Background: 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. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. Methods and result: The 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. Conclusion: Our 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.
Background HCV is a major health problem that infects 350 million people worldwide and 10 million people in Pakistan [1]. 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]. The current standard therapy is Pegylated interferon and ribavirin, which shows poor tolerability and is only capable of attaining a sustained viral response in half of patients due to resistance mutations, adverse side effects and high cost [3]. HCV is a small enveloped virus with a positive-sense, single-stranded RNA genome that encodes a large polyprotein of 3010 amino acids. The polyprotein is co- and post-translationally processed by cellular and virally encoded proteases to produce four structural (Core, E1, E2 and P7) and six non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A, NS5B) [4,5]. Among the structural protein, HCV envelop protein E1 and E2 are highly glycosylated and play an important role in cell entry. HCV NS3 * Correspondence: [email protected] 1 Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan Full list of author information is available at the end of the article
serine protease and NS5b RNA dependent RNA polymerase play an important role in replication. HCV NS3 serine protease, NS5B RNA-dependent RNA polymerase and HCV structural proteins are vital targets for antiviral drug development. Due to the absence of suitable animal model and competent in-vitro cell culture system the mechanism of HCV cell entry was unrevealed a
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