Huang Li-Rung, Wu Hui-Lin, Chen Pei-Jer, Chen Ding-Shinn
Graduate Institute of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital, 1 Chang-Te Street, Taipei 100, Taiwan.
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17862-7. doi: 10.1073/pnas.0608578103. Epub 2006 Nov 9.
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.
需要一种人类乙型肝炎病毒(HBV)耐受的动物模型来研究其机制。该模型还将有助于为现有的3.5亿慢性乙型肝炎患者制定治疗策略。我们通过将工程化的、具有复制能力的HBV DNA经尾静脉水动力注射到C57BL/6小鼠体内,建立了一个小鼠模型。在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可检测到病毒复制中间体、转录本和蛋白质,长达1年。该模型中对HBV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,这在人类中也有记录。这种动物模型将加速对人类慢性乙型肝炎感染的进一步基因和机制研究。