Development of Global Consensus Sequence and Analysis of Highly Conserved Domains of HCV NS5B Protein. [10.5812/hepatmon.6142]
Open Access
- 2 October 2012
- journal article
- Published by Briefland in Hepatitis Monthly
- Vol. 12 (9), e6142
- https://doi.org/10.5812/hepatmon.6142
Abstract
Hepatitis C virus (HCV) is a plus stranded RNA virus which encodes 10 different genes. The HCV NS5B gene encodes a polymerase, which is responsible for the replication of the virus and is a potential target for the development of antiviral agents. HCV has a high mutation rate and is classified into six major genotypes. The aim of this study was to draw a representing consensus sequence of each HCV genotype, align all six consensus sequences to draw a global consensus sequence and also study the highly conserved residues. 236 HCV NS5B sequences, belonging to all six genotypes, reported from all over the world were aligned then a representing phylogenetic tree wasdrawn. The active site residues D220, D225, D318 and D319, which bind the divalent cations, are highly conserved among all the HCV genotypes. The other catalytic pocket residues, R158, S367, R386, and T390 and R394, which interact with the triphosphate of NTPs, are also highly conserved while T390 is mutated to valine in the genotype 5. The motif B residues G283, T286, T287 and N291, which take part in sugar selection by RdRp, are also highly conserved except for T286 which is mutated to proline in the genotypes 3 and 6. The residues E18, Y191, C274, Y276 and H502, which take part in primer/template interaction, are also high conserved except for H502 which is mutated to serine in genotype 2. High variation in all the six consensus sequences was observed in a 12 amino acid beta hairpin loop, which interacts with the double stranded RNA. Nine different peptides from the highly conserved regions of HCV NS5B protein were drawn which can be used as a peptide vaccine. The HCV NS5B phylogenetic tree shows the clusters of different genotypes and their evolutionary association. In spite of a high mutation rate in HCV, the residues which are present in the catalytic pocket, sugar selection and template/primer interaction are highly conserved. These are target sites for the development of antiviral agents or peptide vaccines. The phylogenetic analysis suggests that different HCV genotypes have been evolved from the genotype 1a.Keywords
This publication has 11 references indexed in Scilit:
- NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1bVirology Journal, 2011
- Hepatitis C Virus entry: the early steps in the viral replication cycleVirology Journal, 2009
- Hepatitis C virus in Pakistan: A systematic review ofprevalence, genotypes and risk factorsWorld Journal of Gastroenterology, 2009
- Polymorphisms of some cytokines and chronic hepatitis Band C virus infectionWorld Journal of Gastroenterology, 2009
- Functional and phenotypic characterization of peptide-vaccine-induced HCV-specific CD8+ T cells in healthy individuals and chronic hepatitis C patientsVaccine, 2007
- Investigation of the genotype distribution of hepatitis C virus among Turkish population in Turkey and various European countries.2005
- HCV RNA-dependent RNA polymerase as a target for antiviral development.Current Opinion in Pharmacology, 2002
- Structural Analysis of the Hepatitis C Virus RNA Polymerase in Complex with RibonucleotidesJournal of Virology, 2002
- A Novel Mechanism to Ensure Terminal Initiation by Hepatitis C Virus NS5B PolymeraseVirology, 2001
- Analysis of RNA-Dependent RNA Polymerase Structure and Function as Guided by Known Polymerase Structures and Computer Predictions of Secondary StructureVirology, 1998