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回复 x321 的帖子
他们用几个鼠标模型和基因基因剔除技术, 超出了我所知.
Chronic HBV Infection Can Be Mimicked in a Mouse Model.
We used a previously described method to induce HBV persistence in immunocompetent mice (6). A plasmid containing a 1.2 over length sequence of HBV genotype A was hydrodynamically injected into mice, but in contrast to the previously published protocol, we did not anesthetize animals. Using this modified technique, we did not observe any injection-associated mortality, and C57BL/6 mice showed persistently high serum HBV DNA levels over 8–12 wk (Fig. 1A). Eventually, HBV DNA levels fell in all animals along with the levels of serum HBV surface antigen (HBsAg) (Fig. S1A). The decline in HBV DNA and HBsAg levels coincided with the appearance of anti-HBV antibodies in the serum (Fig. S1B). The initial control of HBV was followed by relapsing and remitting periods of HBV DNA viremia over many months (Fig. 1A). The plasmid backbone used to deliver HBV could not be detected in hydrodynamically injected animals beyond 5 wk after injection (Fig. S1C). These results suggest that the HBV genome persisted as an integrated or episomal form in hepatocytes after the plasmid that was used to induce infection had been cleared. Viral and subviral particles along with HBV e-antigen were detected in the serum, and HBV pregenomic and subgenomic RNAs were present in the livers of hydrodynamically injected animals (Fig. S1 D–F). Mice in which HBV was introduced by hydrodynamic injection began to control HBV DNA levels over a 12-wk period. The control of HBV DNA was associated with a modest, intermittent increase in levels of serum aspartate aminotransferase and alanine aminotransferase that may indicate hepatocyte dysfunction (Fig. S1 G and H). HBV core antigen (HBcAg) was detected in 4–15% of hepatocytes in infected mice using immunofluorescence staining (Fig. 1B). In contrast to C57BL/6 mice, C3H mice (endotoxin-sensitive strain) could not control serum HBV DNA levels and showed persistent viremia for at least 20 wk after induction of infection (Fig. 1C). The cause of the difference in HBV control between the two strains of mice is not clear and warrants additional investigation. Our C57BL/6 mouse model of HBV recapitulated many aspects of human HBV infection, enabling us using gene-targeted mice to dissect host factors that contributed to the initial control of HBV.
慢性HBV感染可在小鼠模型来模拟。
我们使用了先前描述的方法，以诱导在免疫活性小鼠（6）的HBV的持久性。一个包含1.2以上长度的序列的HBV基因型的质粒流体力学注射到小鼠体内，但相较于先前公布的协议，我们没有麻醉的动物。使用这种改良的技术，我们没有观察到任何注射相关的死亡率和C57BL / 6小鼠表现出持续的高血清HBV DNA水平在8-12周（图1A）。最终，HBV DNA水平下降了在所有动物中随着血清HBV表面抗原（HBsAg）（图S1A）的水平。在HBV DNA和HBsAg水平的下降正好与抗乙肝抗体的血清（图S1B）的外观。乙肝病毒的初始控制随后复发和缓解的HBV DNA病毒血症期间在许多个月（图1A）。不能在超过5周流体动力学注射的动物注射（图S1C）之后被检测到用于递送的HBV质粒骨架。这些结果表明，HBV基因组持久保存为在肝细胞中的集成或游离形式被用来诱导感染的质粒已被清理后。随着乙肝e抗原的病毒和亚病毒颗粒的血清中检测到，和HBV前基因组和亚基因组RNA的存在于流体动力学注射的动物（图S1 D-F）的肝脏。小鼠中HBV由高压注射介绍开始控制HBV DNA水平在12周的时间。 HBV DNA的控制用血清谷草转氨酶和谷丙转氨酶，可能表明肝细胞功能障碍（图S1 G和H）的水平适度，间歇的增加相关联。 HBV核心抗原（HBcAg）的免疫荧光染色（图1B）在受感染的小鼠肝细胞的4-15％进行检测。与此相反，以C57BL / 6小鼠，C3H小鼠（内毒素敏感株）不能控制血清HBV DNA水平并表现出持续的病毒血症诱导感染的（图1C）后至少20周。在这两个品系的小鼠之间HBV控制差异的原因尚不清楚，认股权证进一步调查。 HBV我们C57BL / 6小鼠模型概括人类乙肝病毒感染的各个方面，使我们利用基因打靶小鼠剖析促成乙肝病毒的初步控制宿主 |
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楼主: HBVCURER
发表于 2015-5-12 12:32
峰回路转柳暗花明
