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. OBJECTIVES:This study aimed to find and identify some new resistance mutations of HBV from the patients accepted anti-HBV therapy. PATIENTS AND 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.

SUBMITTER: Qin B 

PROVIDER: S-EPMC3842524 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature