Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Int J Oncol. 2011 Dec;39(6):1511-9. doi: 10.3892/ijo.2011.1145. Epub 2011 Jul 28.
A relevant animal model is critical for investigating the pathogenic mechanisms underlying hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Mice are not naturally infected by HBV, presumably due to the lack of HBV receptors on mouse hepatocytes. To bypass this entry step of HBV infection, we report generation of a novel HBV model in immunocompetent mice by hepatic delivery of the HBV genome using trans-splicing adeno-associated viral vectors (AAV/HBV). We confirmed production of HBV virions and proteins in the liver and circulation in all AAV/HBV-transduced mice in all four immunocompetent mouse strains tested. These mice produced antigen and antibody profiles similar to that observed in chronic HBV patients. Importantly, 12-16 months later, all 12 AAV/HBV-transduced mice developed macroscopically visible liver-tumor nodules. Ten of the twelve tumors were characterized with typical HCC features. This AAV/HBV-transduced murine HCC model provides a useful instrument for studying the pathogenesis of HBV-associated HCC and the development of HCC therapeutic interventions.
一个相关的动物模型对于研究乙型肝炎病毒（HBV）引起的肝细胞癌（HCC）的发病机制至关重要。由于缺乏小鼠肝细胞上的 HBV 受体，因此小鼠不会自然感染 HBV。为了绕过 HBV 感染的这个进入步骤，我们报告了一种通过使用反式拼接腺相关病毒载体（AAV/HBV）在免疫活性小鼠中进行肝内传递 HBV 基因组来产生新型 HBV 模型。我们证实了在所有四种免疫活性小鼠品系中，所有接受 AAV/HBV 转导的小鼠的肝脏和循环中都产生了 HBV 病毒颗粒和蛋白。这些小鼠产生的抗原和抗体谱与慢性 HBV 患者观察到的相似。重要的是，12-16 个月后，所有 12 只接受 AAV/HBV 转导的小鼠均出现了肉眼可见的肝肿瘤结节。12 个肿瘤中有 10 个具有典型的 HCC 特征。这种 AAV/HBV 转导的小鼠 HCC 模型为研究 HBV 相关 HCC 的发病机制和 HCC 治疗干预措施的发展提供了有用的工具。
