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Quasispecies And Codon Usage Analysis Of HBV

Posted on:2017-09-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Y GongFull Text:PDF
GTID:1364330614960888Subject:Internal Medicine
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Hepatitis B virus is a major threat to global public health.There are more than three hundred million carriers worldwidely.In China hepatitis B virus and liver cancer are related in most times.Hepatitis B vaccine greatly reduces the hepatitis B virus infection,but there are still vaccination failures and immune escape.In clinical treatment of hepatitis B virus depends on nucleic acid analog,but with the time of treatment,the probability of the virus resistant mutations dramatically increased.High mutant rate of hepatitis B virus makes it easy to produce large amounts of viral quasispecies,and the gene's information of immune escape mutations and drug resistance are hided in the quasispecies of hepatitis B virus.To study the quasispecies,we use a series of bioinformatics methods to analyze sequences of HBV in different clinical states.In the analysis of HBV quasispecies diversity in the MTCT,we use transposon enzyme to interrupt HBV genome.With the second-generation sequencing technology,four pairs of mother and son with HBV infection were analyzed.The results showed that the quasispecies between mother and son are high homology.A large number of insertion and deletion were detected in the coding region,while ? decision clusters related to immune escape mutations occur mostly in the low-frequency quasispecies.These results imply the existence of quasispecies complementary mechanisms of viruses.In the analysis of HBV genotype variations in ADV treatment,we analyzed 218 HBV patients.The genotypes before and after a year ADV treatment were counted.We studied mixing ratio under different clinical conditions,such as E antigen,liver function,drug sensitivity.The results showed that genotype C was much more sensitive than genotype B.In addition,after 48 weeks treatment,genotypes in E antigen transformed and non-transformed patient were greatly changes.Study on codon usage of HBc and HBx.In order to obtain an accurate picture of codon usage in different cross-section of different clinical state,we calculate correlation of codon usage of two regions.The results showed that chronic hepatitis B,there is a big difference among chronic hepatitis,cirrhosis and liver cancer.A huge change in HBx codon bias of cirrhotic patients occurred.Codon usage analyze of reverse transcriptase region in hepatitis B virus in adefovir therapy.We calculated the codon usage of HBV RT region of 48 ADV treated patients with HBV.Correspondence analysis shows that before and after ADV treatment there is an enormous shift of codon usage.Correlation analysis of liver cytokines and HBV RT region showed that correlation between cytokines and HBV after ADV treatment increased.My experiments used several methods of bioinformatics,studied the HBV gene information from different angles in different clinical states.
Keywords/Search Tags:HBV, quasispecies, codon usage
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