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Hepatitis C Virus Genotyping And Epitope Prediction Based On Genotype

Posted on:2010-06-03Degree:MasterType:Thesis
Country:ChinaCandidate:X H WanFull Text:PDF
GTID:2144360278965043Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide, with more than 170 million individuals with chronic infection. HCV infection rate is 3.2% and there are approximately 38 million infected persons in china. It is estimated that on average 20% of those with chronic HCV will develop liver cirrhosis over a 20-year period after infection, although the range is highly variable; and of those who develop cirrhosis between 1% and 5% will develop hepatocellular carcinoma over a 30-year period after infection. The current standard of treatment of HCV is a combination therapy with pegylated IFNαand ribavirin. Overall sustained virologic response (SVR), defined as the absence of virus in the blood 24 weeks after therapy is ended, in about 50% of chronic infected patients treated with combination therapy. Therefore, it is great significant to develop the safe and effective preventive and therapeutic HCV vaccine.Multivalent HCV epitope vaccine has been a new research trend in recent years. These studies express HCV epitope protein by the methods of chemical synthesis or gene cloning, which are based on epitope prediction. This paper proposes an idea that HCV vaccine development is necessary according to the characteristics of the genome variation and genotype distribution. This study systematically analyzed the HCV epitope of the major genotypes in china by the way of bioinformaitocs.Due to HCV RNA polymerase is lack of correction function, the result is that there is a high genomic heterogeneity. In accordance with the extent of genome variation HCV can be divided into at least six genotypes, the genotype can be divided into several subtypes. It is now clear that HCV genotype is closely related with the severity of liver disease, liver cancer incidence and treatment effect. However, HCV genotyping has a wide range of methods which is based on different regions of HCV. The gold standard does not yet set up. In order to establish the rationale for genotypic determination of optimal region sequence, Phylogenetic trees on 5′UTR, core, E1, E2 and NS5B region were reconstructd. It is demonstrated that the NS5B area is the best genotyping region instead of the complete genome sequence, which is the first time using the method of bioinformatics.HCV genotypes 1b and 2a are main in china, while genotype 6a is a larger proportion at Hong Kong, Macao and the border provinces of southwest china. In this paper, the second part predicted and analyzed the three genotypes of HCV whose B cell epitopes, CD8 + T cell epitopes and CD4 + T cell epitopes. To undergo a rigorous screening assessment, gain the protein location and amino acid sequence of the dominant epitopes which can be used to develop the HCV multiepitope vaccine. The third part of the study created a software, HCV epitope to assess system, which can extracts the amino acid residues and the corresponding protein secondary structure of the HCV epitope and calculates the average antigen index score. The software can save, inquiry and analyze the epitopes and design the multiepitope vaccine.
Keywords/Search Tags:Hepatitis C Virus, epitope vaccine, genotype, bioinformatics
PDF Full Text Request
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