A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice.
A new model mimicking persistent HBV e antigen-negative infection using covalently closed circular DNA in immunocompetent mice.
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使用共价闭合环状 DNA 在免疫活性小鼠体内模拟持续性 HBV e 抗原阴性感染的新模型
DOI：
10.1371/journal.pone.0175992
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lai GQ
中科院分区：
文献类型：
--
作者：
Wang L;Cao M;Wei QL;Zhao ZH;Xiang Q;Wang HJ;Zhang HT;Lai GQ
尽管有有效的疫苗，但B型肝炎病毒（HBV）感染仍然是一个主要的健康问题。乙型肝炎病毒e抗原（HBeAg）阴性株已成为流行。以前，没有动物模型模拟HBeAg阴性HBV感染的临床过程。为了建立HBeAg阴性HBV感染模型，从临床样品中克隆HBeAg阴性HBV的3.2-kb全长基因组，然后环化以形成共价闭合环（cccDNA）。通过流体动力学注射将所得cccDNA引入C57 BL/6 J小鼠的肝脏中。使用HBV特异性标志物（包括HBV表面抗原（HBsAg）、HBeAg和HBV核心抗原（HBcAg）以及DNA拷贝）在预定时间点监测HBeAg阴性感染的持续性。在整个研究中，使用pAAV-HBV 1.2作为对照。在注射HBeAg阴性cccDNA的小鼠中，HBV感染率在初始阶段为100%。HBsAg水平增加至1周，在该点水平达到峰值，此后迅速下降。在60%的注射小鼠中，HBsAg和HBcAg持续超过10周。在血清和肝脏中检测到大量HBV DNA拷贝。此外，cccDNA持续存在于HBeAg阴性小鼠的肝组织中。与注射pAAV-HBV 1.2的小鼠相反，在整个研究期间，在注射HBeAg阴性HBV的小鼠中未发现HBeAg。这些结果证明了在免疫活性小鼠中首次成功建立HBeAg阴性HBV持续感染模型。与pAAV-HBV 1.2组相比，模型组小鼠感染持续时间和血清病毒学及生化指标水平基本相同。该模型将有助于HBeAg阴性HBV感染的机制研究，并有助于评价新的抗病毒药物。
Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem. HBV e antigen (HBeAg)-negative strains have become prevalent. Previously, no animal model mimicked the clinical course of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a clinical sample and then circularized to form covalently closed circular (cccDNA). The resulting cccDNA was introduced into the liver of C57BL/6J mice through hydrodynamic injection. Persistence of the HBeAg-negative infection was monitored at predetermined time points using HBV-specific markers including HBV surface antigen (HBsAg), HBeAg, and HBV core antigen (HBcAg) as well as DNA copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage. HBsAg levels increased up to 1 week, at which point levels peaked and dropped quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more than 10 weeks. High numbers of HBV DNA copies were detected in the serum and liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected with HBeAg-negative HBV throughout the study period. These results demonstrate the first successful establishment of a model of HBeAg-negative HBV-persistent infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the infection persistence and levels of serum virological and biochemical markers were approximately equal in the model mice. This model will be useful for mechanistic studies on HBeAg-negative HBV infection and will facilitate the evaluation of new antiviral drugs.
影响因子：
3.4
作者：
Lai G;Zhang W;Tang H;Zhao T;Wei L;Tao Y;Wang Z;Huang A
通讯作者：
Huang A