title: Substitution rtq267h of hepatitis B virus increases the weight of replication and Lamivudine resistance.
abstract: BACKGROUND
  Nucleus(t)ide analogs (NAs), containing Lamivudine (LMV), adefovir dipivoxil (ADV), endeavor (ETV), telbivudine (LdT), and tenofovir (TDF) are widely used for the treatment of chronic hepatitis B (CHB), but long term anti-Hepatitis B virus (HBV) therapy with NAs may give rise to the emergence of drug-resistant viral mutants.
  
  
  OBJECTIVE
  This study aimed to find and identify some new resistance mutations of HBV from the patients accepted anti-HBV therapy.
  
  
  METHODS
  The reverse transcriptase (RT) coding region of HBV was PCR-amplified using HBV DNA extracted from patients' blood samples and sequenced.
  
  
  RESULTS
  Nineteen substitution mutations were detected. Among them, rtQ267H was often observed in patients receiving LMV administration. This LMV therapy-related mutation was introduced into HBV replication-competent plasmids. The in vitro susceptibility of both wild-type (WT) and mutant-type (MT) HBV to NAs was analyzed by Southern blot, and/or quantitative real-time PCR (qRT-PCR). The rtQ267H substitution enhanced HBV replication not merely in single-site mutation, but also in multisite mutations. The in vitro susceptibility analysis showed that the existence of rtQ267H in WT and LMV-resistant (LMVr) HBV were responsible for the reduced susceptibility to LMV to varying degrees, and enhanced HBV replication capacity. However, HBV harbored this substitution retained normal susceptibility to ADV, LdT, ETV, and TDF.
  
  
  CONCLUSIONS
  The result suggested that rtQ267H is a potential adaptive mutation of HBV to LMV.
authors.affiliation: Shaoxing Centre for Disease Control and Prevention, Shaoxing, China ; State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Life Science, Shaoxing University, Shaoxing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shaoxing Centre for Disease Control and Prevention, Shaoxing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: He
authors.affiliation: Shaoxing Centre for Disease Control and Prevention, Shaoxing, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Xu
authors.affiliation: Shaoxing Centre for Disease Control and Prevention, Shaoxing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Fu
authors.affiliation: Shaoxing Centre for Disease Control and Prevention, Shaoxing, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Tu
keywords: Hepatitis B Virus; Mutation; Susceptibility