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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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Title HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy
 
Creator Banerjee, Priyanka
Chakraborty, Abhijit
Mondal, Rajiv Kumar
Khatun, Mousumi
Datta, Somenath
Das, Kausik
Pandit, Pratap
Mukherjee,, Souvik
Banerjee, Soma
Ghosh, Saurabh
Chakrabarti, Saikat
Chowdhury, Abhijit
Datta, Simanti
 
Subject Structural Biology & Bioinformatics
 
Description 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-naïve 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.
 
Date 2017-03-17
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2638/1/Scientific_Reports_%2C2017.pdf
Banerjee, Priyanka and Chakraborty, Abhijit and Mondal, Rajiv Kumar and Khatun, Mousumi and Datta, Somenath and Das, Kausik and Pandit, Pratap and Mukherjee,, Souvik and Banerjee, Soma and Ghosh, Saurabh and Chakrabarti, Saikat and Chowdhury, Abhijit and Datta, Simanti (2017) HBV quasispecies composition in Lamivudine-failed chronic hepatitis B patients and its influence on virological response to Tenofovir-based rescue therapy. Scientific Reports, 7 (44742). 01p.-13p..
 
Relation http://dx.doi.org/10.1038/srep44742
http://www.eprints.iicb.res.in/2638/