Phylogenetic inference for the dynamics of within-host HBV replication in patients with poor response to nucleos(t)ide analogues treatment
YU Tong
ZHANG Miaoqu
ZHANG Qiran
ZHENG Jianming
SHEN Chuan
ZOU Lei
QIU Chao
ZHANG Wenhong
MENG Zhefeng
Abstract：Objective To investigate the dynamic changes of HBV in patients with poor response to nucleos(t)ide analogues(Nas)treatment in order to guide the synthesis of new drugs and the adjustment of treatment.Methods Serum HBV RNA from patient at multiple longitudinal time points(≥2,at least 3 months apart)was extracted,high-throughput sequenced was carried out to construct phylogenetic trees,calculate genetic distances,and analyze virus resistance in order to study the dynamics of viral replication.Results The evolution trends of virus and the resistance mutant were consistent with the change of serum HBV DNA in patients with poor response to Nas treatment.While the maximum-likelihood tree(ML-Tree)was more suitable for inferring viral replication,and the neighbor-joining tree(NJ-Tree)more suitable for inferring the proliferation of infected hepatocytes,and the persistence of the same variants were observed in patients with poor response to Nas treatment.Conclusion Phylogenetic analysis can detect the dynamics of HBV in the host,and the appropriate tree-building method should be selected according to the research purpose.
Keywords：HBVphylogeneticsviral replicationclone expansionnucleos(t)ide analoguesantivirals
Publication Date：2023-10-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 385-391 )