The infection efficiency and replication ability of circularized HBV DNA optimized the linear HBV DNA in vitro and in vivo.

The infection efficiency and replication ability of circularized HBV DNA optimized the linear HBV DNA in vitro and in vivo.
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环状 HBV DNA 的感染效率和复制能力在体外和体内优化了线性 HBV DNA。

DOI:
10.3390/ijms16035141
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发表时间:
2015-03-05
影响因子:
5.6
通讯作者:
Huang A
Huang A
中科院分区:
生物学2区
文献类型:
--
作者:
Li X;Zhu J;Lai G;Yan L;Hu J;Chen J;Tang N;Huang A

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由于缺乏可靠的动物模型,对乙型肝炎病毒持续感染的分子机制的研究一直受到阻碍。我们成功地建立了一个简单、通用、可重复的体外和体内HBV持续感染模型。细胞和小鼠分别转染或注射环状HBV DNA和pAAV/HBV1.2。在指定时间采集细胞、上清液、血清和肝组织进行病毒学和血清学检测。在体外和体内,环状HBV DNA和pAAV/HBV1.2均能高效复制和转录,但前者的感染效果优于后者(p < 0.05)。将循环化HBV基因组DNA注射到小鼠体内,可强力支持HBV感染,约80%的HBV感染小鼠建立了至少10周的持续感染。本研究表明,在体外和体内,环状结构HBV DNA的感染效率和复制能力优于含有线性结构HBV DNA的表达质粒。同时,本研究结果可为进一步研究人慢性HBV感染的致病机制和潜在的体内外抗病毒治疗提供有用的工具和方法。
Studies on molecular mechanisms of the persist infection of hepatitis B virus have been hampered by a lack of a robust animal model. We successfully established a simple, versatile, and reproducible HBV persist infection model in vitro and in vivo with the circularized HBV DNA. The cells and mice were transfected or injected with circularized HBV DNA and pAAV/HBV1.2, respectively. At the indicated time, the cells, supernatants, serum samples, and liver tissues were collected for virological and serological detection. Both in vitro and in vivo, the circularized HBV DNA and pAAV/HBV1.2 could replicate and transcribe efficiently, but the infection effect of the former was superior to the latter (p < 0.05). The injection of circularized HBV genome DNA into the mice robustly supported HBV infection and approximately 80% of HBV infected mice established persistent infection for at least 10 weeks. This study demonstrated that the infection efficiency and replication ability of the circularized structure of HBV DNA overmatched that of the expression plasmid containing the linear structure of HBV DNA in vitro and in vivo. Meanwhile, this research results could provide useful tools and methodology for further study of pathogenic mechanisms and potential antiviral treatments of human chronic HBV infection in vitro and in vivo.
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