An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infection
An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infection
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DOI：
10.1073/pnas.0608578103
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发表时间：
2006-11-21
影响因子：
11.1
通讯作者：
Chen, Ding-Shinn
中科院分区：
文献类型：
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作者：
Huang, Li-Rung;Wu, Hui-Lin;Chen, Ding-Shinn
需要建立人类乙型肝炎病毒（HBV）耐受性的动物模型来研究其机制。该模型还将促进现有 3.5 亿慢性乙型肝炎患者的治疗策略。我们通过将工程化的、具有复制能力的 HBV DNA 注射到 C57BL/6 小鼠的尾静脉中，建立了小鼠模型。 40% 的注射小鼠中，HBV 表面抗原血症持续超过 6 个月。在注射小鼠的肝脏组织中检测到病毒复制中间体、转录本和蛋白质长达一年。该模型中对乙型肝炎表面抗原的耐受性被证明是由于针对乙型肝炎核心抗原的细胞免疫不足，正如在人类中所记录的那样。该动物模型将加速人类慢性乙型肝炎感染的进一步遗传和机制研究。
An animal model for human hepatitis B virus (HBV) tolerance is needed to investigate the mechanisms. This model will also facilitate therapeutic strategies for the existing 350 million patients with chronic hepatitis B. We established a mouse model by hydrodynamic injection of an engineered, replication-competent HBV DNA into the tail veins of C57BL/6 mice. In 40% of the injected mice, HBV surface antigenemia persisted for > 6 months. Viral replication intermediates, transcripts, and proteins were detected in the liver tissues of the injected mice for up to 1 year. The tolerance toward HBV surface antigen in this model was shown to be due to an insufficient cellular immunity against hepatitis B core antigen, as was documented in humans. This animal model will accelerate further genetic and mechanistic studies of human chronic hepatitis B infection.