Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure
Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure
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DOI：
10.1016/j.jhep.2008.01.027
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发表时间：
2008-05-01
影响因子：
25.7
通讯作者：
Zoulim, Fabien
中科院分区：
文献类型：
--
作者：
Villet, Stephanie;Pichoud, Christian;Zoulim, Fabien
背景/目标：最近的临床观察报告了HBV聚合酶181位氨基酸替换的发生，与拉米夫定或阿德福韦治疗下的病毒突破有关。在这项研究中，我们的特点是主要的变种窝藏rtA 181 T/V突变分离的10个连续的患者谁开发拉米夫定和/或阿德福韦resistance.Methods：我们进行了一个克隆分析的HBV聚合酶基因扩增的血清样本在病毒突破。结果：在拉米夫定、阿德福韦或拉米夫定+阿德福韦突破后，rtA 181 T/V与rtN 236 T共定位于同一HBV基因组，而与rtM 204 V/I突变无共定位。在细胞培养中，rtA 181 T/V突变诱导了对拉米夫定敏感性的降低（
Background/Aims: Recent clinical observations reported the occurrence of amino acid substitutions at position 181 of the HBV polymerase, associated with a viral breakthrough under lamivudine or adefovir therapy. In this study, we characterized the main variants harboring the rtA181T/V mutation isolated from 10 consecutive patients who developed lamivudine and/or adefovir resistance.Methods:We performed a clonal analysis of the HBV polymerase gene amplified by PCR from serum samples during viral breakthrough. The main mutants were then tested after transfection of Huh7 cells for their resistance profile to nucleoside analogs.Results:Clonal analysis revealed the co-localization on the same HBV genome of rtA181T/V with rtN236T, but not with rtM204V/I mutations following lamivudine, adefovir or lamivudine + adefovir breakthrough. In cell culture, the rtA181T/V mutation induced a decreased susceptibility to lamivudine (