Characterization of HCV Genotype 5a Envelope Proteins: Implications for Vaccine Development and Therapeutic Entry Target

摘要

Background: Hepatitis C virus (HCV) is one of the major causes of cirrhosis and hepatocellular carcinoma with an estimation of 185 million people with infection. The E2 is the main target for neutralizing antibody responses and the variation of this region is related to maintenance of persistent infection by emerging escape variants and subsequent development of chronic infection. While both E1 and E2 are hypervariable in nature, it is difficult to design vaccines or therapeutic drugs against them. Objectives: The objective of this study was to characterize genotype 5a E1 and E2 sequences to determine possible glycosylation sites, conserved B-cell epitopes and peptides in HCV that could be useful targets in design of vaccine and entry inhibitors. Patients and Methods: This study was conducted through PCR amplification of E1 and E2 regions, sequencing, prediction of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18 samples of HCV genotype 5a from South African. Results: Differences in the probability of glycosylation in E1 and E2 regions were observed in this study. Three conserved antigenic B-cell epitopes were predicted in the E2 regions and also 11 short peptides were designed from the highly conserved residues. Conclusions: This study provided conserved B-cell epitopes and peptides that can be useful for designing entry inhibitors and vaccines able to cover a global population, especially where genotype 5a is common.