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Classification Of Naturally Occuring HBV Variants Possessing Potential Growth Advantage And Identification Of Intergenotypic Recombinations In HAV And DHBV

Posted on:2011-07-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:W LiuFull Text:PDF
GTID:1114360305497262Subject:Pathogen Biology
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Hepatitis B virus (HBV) is a worldwide pandemic virus. Currently, more than 2 billion people have been infected with HBV, of which about 450 million people are chronic carriers.1 million human death results from acute or chronic consequences of hepatitis B. About 25% of chronic carriers who acquired HBV infection during childhood die later of cirrhosis or liver cancer.In the present study,3044 complete HBV genomic sequences from GenBank were systematically analyzed by bioinformatic methods. The results identified 32 types of HBV deletion or insertion variants, which might possess potential growth advantage. In these mutant strains, the deletions of large segments (eg:1256bp deletion,183bp deletion) in the HBV genome strictly follow the GT-AG rule, while the deletions of small segments (eg:96bp deletion,54bp deletion,6bp deletion) do not follow the GT-AG rule. Furthermore, many strains harbor mutations of vaccine escape and/or drug-resistance.We then established a simple yet specific method, which can detect the HBV viral DNA in the cells. By using this method, we found that Typeâ… mutant strains, the shortest in all the types, might be able to form rcDNA. The identification and characterization of the HBV mutant strains, which might possess potential gowth advantage, will not only deepen our understanding of the life cycle of HBV but also provide many interesting hints for future basic and clinical studies of HBV.Genetic recombination is a ubiquitous biology process and an important evolutionary mechanism. Recombination between different genotypes is one of many ways for a virus to gain genetic diversity and is considered to play an important role in the evolution of viruses.Co-circulation of subgenotypes IA and IB of Hepatitis A Virus (HAV) has been reported in South Africa, South America, Europe and US. In this study, phylogenetic and recombination analysis was performed for the first time on 31 complete HAV genomes from infected human and simians. Three significant inter-subgenotype recombination events (â… -â…¢) were identified by recombination detection analysis. These results demonstrate that humans can be infected with different HAV subgenotypes and provide valuable hints for future research on HAV diversity.Due to its high similarity to human hepatitis B virus (HBV), duck HBV (DHBV) is often used as an important model for HBV research. While inter-genotypic recombination of HBV is common, it has not been reported with DHBV. In this study, 32 non-redundant DHBV complete genomes were analyzed using phylogenetic methods and classified into two clusters, corresponding to the'Chinese'and'Western country'branches previously reported based on geographical distribution. One 'Chinese'branch strain was isolated in Australia and three'Western country'branch strains were isolated in China, suggesting cross-geographical distribution of both branches. Recombination analyses of the 32 DHBV genomes identified two inter-genotypic recombination events with high confidence value. The identification of inter-genotypic recombination among circulating DHBV isolates suggests the usefulness of DHBV as a model for studying the mechanism of HBV recombination.
Keywords/Search Tags:Hepatitis B Virus, variants, drug resistance, vaccine escape, Hepatitis A virus, Duck Hepatitis B Virus, complete genomic sequence, recombination
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