Impact of hepatitis B e antigen-suppressing mutations on the replication efficie

StephenW

<http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01378.x/abstract>

Impact of hepatitis B e antigen-suppressing mutations on the replication
efficiency of entecavir-resistant hepatitis B virus strains

S. Amini-Bavil-Olyaee, U. Herbers, T. Luedde, C. Trautwein, F. Tacke

Article first published online: 30 SEP 2010

DOI: 10.1111/j.1365-2893.2010.01378.x

© 2010 Blackwell Publishing Ltd
Issue
Journal of Viral Hepatitis
Volume 18, Issue 11, pages 804–814, November 2011

Summary.  Hepatitis B e antigen (HBeAg)-negative hepatitis B commonly
requires long-term treatment with nucleos(t)ide analogues aiming at
persistently suppressing hepatitis B virus (HBV) replication to halt
progression of liver disease and prevent complications. Entecavir (ETV) is
widely used in HBeAg-negative hepatitis B, but distinct HBV polymerase
mutations can confer resistance against ETV, in conjunction with lamivudine
resistance. Precore (PC) and basal core promoter (BCP) mutations that
underlie HBeAg-negativity enhance replication of lamivudine-resistant
mutants. To comprehensively analyse the impact of PC or BCP mutations on
viral replication of ETV-resistant HBV mutants, replication-competent HBV
constructs were generated harbouring lamivudine resistance
(rtM204V/rtL180M, rtM204I) plus ETV resistance (rtS202G, rtS202I or
rtT184G) on wild-type (WT)-, PC- and BCP-backgrounds. Functional
consequences on viral fitness and susceptibility to antivirals were
assessed in vitro. The presence of any ETV resistance drastically reduced
viral replication when compared to WT HBV. In rtS202G mutants (plus
lamivudine resistance), addition of either PC or BCP mutations moderately
enhanced the reduced replication, without reaching WT HBV levels. In
rtS202I or rtT184G mutants, PC and BCP mutations did not significantly
improve viral fitness. All ETV-resistant constructs, independently of PC or
BCP mutations, showed resistance towards ETV and lamivudine, but remained
susceptible to tenofovir. Our data demonstrate that HBeAg-suppressing PC or
BCP mutations cannot restore the strongly reduced replicative capacity of
ETV-resistant HBV mutants to WT level, although they moderately increase
replication of rtS202G combination mutants. ETV resistance thereby differs
from lamivudine resistance alone, corroborating that ETV is in short term a
safe option for HBeAg-negative patients.



(6.合.彩).足球.篮球...各类投注开户下注

第一投注.现金网:招代理年薪10万以上:6668.cc

StephenW

谷歌翻译是不是100％正确，仅供参考，使用。

复制的乙肝e抗原抑制突变mpact
恩替卡韦耐药的乙肝病毒株的效率

C. S.阿米尼- Bavil - Olyaee，U. Herbers，T. Luedde，特劳特魏因，楼Tacke

文章首先在网上公布：2010年09月30日

DOI：10.1111/j.1365-2893.2010.01378.x

© 2010布莱克韦尔出版有限公司
发行
中国病毒性肝炎
第18卷第11期，第804-814页，2011年11月

摘要。乙型肝炎e抗原（HBeAg）的负面乙肝常用
需要长期治疗的核苷（酸）IDE类似物瞄准
持续抑制乙肝病毒（HBV）复制停止
肝脏疾病的进展，防止并发症。恩替卡韦（ETV）
广泛应用于HBeAg阴性B型肝炎，但不同的HBV聚合酶
突变可赋予对教育电视的阻力，在与拉米夫定联合
阻力。前C区（PC）和基础核心启动子（BCP）突变
拉米夫定耐药的HBeAg负的基础，增强复制
突变体。要全面分析PC或BCP突变的影响
ETV抗乙肝病毒的突变体，复制能力的HBV病毒复制
构建窝藏拉米夫定耐药性产生
（rtM204V/rtL180M，rtM204I）加上教育电视电阻（rtS202G，rtS202I或
rtT184G）对野生型（WT） - ，PC和BCP背景。功能
抗病毒药物病毒健身和易感性的后果
在体外评估。存在任何ETV阻力大幅减少
时相比，WT乙肝病毒复制。在rtS202G突变体（加
拉米夫定耐药），任一PC或BCP突变除了适度
增强了减少的复制，没有达到野生型HBV的水平。在
rtS202I或rtT184G突变体，PC和BCP突变没有显著
提高病毒健身。所有教育电视耐构造独立的PC，或
口岸突变，表现为对教育电视和拉米夫定的阻力，但仍
容易以替诺福韦。我们的数据表明，HBeAg抑制的PC或
BCP的突变不能恢复的强烈复制能力降低
ETV耐药HBV突变体为WT的水平，虽然他们适度增加
rtS202G组合突变体的复制。教育电视的阻力，从而不同
从单独拉米夫定耐药性，确证，教育电视在短期内是一个
HBeAg阴性患者的安全选项。