Biological characteristics comparison of HBV rtA181T mutants with truncated or substituted HBsAg expression in vitro and in vivo model systems.
Biological characteristics comparison of HBV rtA181T mutants with truncated or substituted HBsAg expression in vitro and in vivo model systems.
复制标题
HBsAg表达截短或取代的HBV rtA181T突变体体外和体内模型系统的生物学特性比较
DOI：
10.1038/srep39260
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发表时间：
2016-12-15
影响因子：
4.6
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Zhou LY;Chen EQ;Wang ML;Chen LL;Liu CP;Zeng F;Tang H
长期抗病毒治疗时选择乙型肝炎病毒（HBV）聚合酶rtA181T突变。由于聚合酶基因与包膜（S）基因完全重叠，HBV rtA181T突变也携带sW172突变。在本研究中，我们研究了 rtA181T/sW172*（编码截短的 HBsAg）和 rtA181T/sW172L（编码取代的 HBsAg）突变体之间是否存在生物学差异。在细胞实验中，与野生型毒株相比，两种突变株的病毒复制均略有下降，但rtA181T/sW172*中的上清液HBsAg和HBV DNA水平显着低于rtA181T/sW172L转染细胞中的水平。在动物实验中，我们惊奇地发现rtA181T/sW172*突变株的病毒复制量比rtA181T/sW172L突变株明显增加并维持时间显着更长，而rtA181T/sW172L与野生型株之间没有观察到显着差异。与野生型菌株相比，rtA181/sW172*细胞内存在HBsAg和HBcAg积累，而rtA181/sW172L突变菌株则没有细胞内积累。重要的是，我们还发现截短的 HBsAg 可以增加 HBV 核心启动子的活性，但取代的 HBsAg 则不能。综上所述，上述两种rtA181T突变体的特征存在显着差异，区分sW172*截短突变和sW172L取代突变是必要且重要的。
The hepatitis B virus(HBV) polymerase rtA181T mutation is selected during long-term antiviral therapy. As the polymerase gene completely overlaps with the envelope (S) gene, HBV rtA181T mutation also carries sW172 mutations. In this study, we investigated whether there were biological differences between rtA181T/sW172* (coding truncated HBsAg) and rtA181T/sW172L (coding substituted HBsAg) mutants. In cell experiments, a slight decline of viral replication was observed in both two mutants as compared to wild-type strains, but the levels of supernatant HBsAg and HBV DNA in rtA181T/sW172* were significantly lower than those in rtA181T/sW172L transfected cells. In animal experiments, we were amazed to find that viral replication in rtA181T/sW172* mutant increased and maintained significantly longer than that in rtA181T/sW172L mutant, while no significant difference was observed between rtA181T/sW172L and wild-type strains. Compared with wild-type strains, there were intracellular accumulations of HBsAg and HBcAg in rtA181/sW172* but none in rtA181/sW172L mutant strains. Importantly, we also found that truncated HBsAg could increase the activity of HBV core promoter, but substituted HBsAg could not. In summary, the characteristics of above two rtA181T mutants mentioned above were significantly different, and it is necessary and important for us to distinguish sW172* truncated mutation from sW172L substituted mutation.
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