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Basic Characteristics of Mutations
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Mutation Site
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R266I |
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Mutation Site Sentence
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Table 17 |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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P
|
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Genotype/Subtype
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D |
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Viral Reference
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GQ205378
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Functional Impact and Mechanisms
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Disease
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Hepatitis B, Chronic
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
|
- |
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Location
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India |
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Literature Information
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PMID
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28303969
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Title
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HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy
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Author
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Banerjee P,Chakraborty A,Mondal RK,Khatun M,Datta S,Das K,Pandit P,Mukherjee S,Banerjee S,Ghosh S,Chakrabarti S,Chowdhury A,Datta S
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Journal
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Scientific reports
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Journal Info
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2017 Mar 17;7:44742
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Abstract
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The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed chronic hepatitis B (CHB) patients and its impact in defining the subsequent virological responses to Tenofovir (TDF)-based rescue-therapy. By analyzing HBV clones encompassing reverse transcriptase (RT) and surface (S) region from LMV-failed and treatment-naive CHB patients, we identified 5 classical and 12 novel substitutions in HBV/RT and 9 substitutions in immune-epitopes of HBV/S that were significantly associated with LMV failure. In silico analysis showed spatial proximity of some of the newly-identified, mutated RT residues to the RT catalytic centre while most S-substitutions caused alteration in epitope hydrophobicity. TDF administration resulted in virological response in 60% of LMV-failed patients at 24-week but non-response in 40% of patients even after 48-weeks. Significantly high frequencies of 6 S-substitutions and one novel RT-substitution, rtH124N with 6.5-fold-reduced susceptibility to TDF in vitro, were noted at baseline in TDF non-responders than responders. Follow-up studies depicted greater evolutionary drift of HBV quasispecies and significant decline in frequencies of 3 RT and 6 S-substitutions in responder-subgroup after 24-week TDF-therapy while most variants persisted in non-responders. Thus, we identified the HBV-RT/S variants that could potentially predict unfavorable response to LMV/TDF-therapy and impede immune-mediated viral clearance.
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Sequence Data
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-
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