ACUTE HEPATITIS IN RATS EXPRESSING HUMAN HEPATITIS-B VIRUS TRANSGENES
ACUTE HEPATITIS IN RATS EXPRESSING HUMAN HEPATITIS-B VIRUS TRANSGENES
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DOI：
10.1073/pnas.92.5.1470
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发表时间：
1995-02-28
影响因子：
11.1
通讯作者：
ISSELBACHER, KJ
中科院分区：
文献类型：
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作者：
TAKAHASHI, H;FUJIMOTO, J;ISSELBACHER, KJ
导致肝细胞死亡的分子机制以及在乙肝病毒感染中导致病毒清除的事件还不是很清楚，但由于在体外感染人肝细胞的困难和缺乏合适的动物模型，导致相关机制的阐明变得复杂。我们报道了一种体内转染人乙肝病毒的动物模型。我们用膜融合促进型阳离子脂质直接将复制能力强的克隆的HBVDNA载体导入大鼠肝脏，用这种体内转染法在大鼠肝脏中表达了HBVmRNA和3.2kb的HBVDNA，在大多数大鼠体内，在3-7天后的血液中发现了HBV病毒粒子和HBe抗原，之后出现了针对e抗原的抗体。转染后2~3周，血清谷丙转氨酶水平升高，肝门静脉周围可见肝细胞死亡和淋巴细胞浸润，血清中未检测到HBV病毒粒子。因此，将REV基因导入大鼠体内，可引起类似于乙肝病毒所致的急性肝炎的组织学和血清学改变，而在T淋巴细胞缺陷的裸鼠体内，未见肝细胞损伤，病毒血症明显延长，为T淋巴细胞在肝细胞损伤和清除病毒的过程中发挥重要作用提供了直接证据，该大鼠肝炎模型可用于研究乙肝病毒感染的发病机制。
The molecular mechanisms responsible for hepatocyte death and the events leading to viral clearance in hepatitis B virus (HBV) infections are not well understood, Elucidation of the mechanisms involved have been complicated by the difficulty of infecting human hepatocytes with HBV in vitro and the lack of an appropriate animal model. We report an animal model of human HBV infection by in vivo transfection. We have directly introduced a replication-competent, cloned HBV construct into rat liver by using a membrane fusion-promoting cationic lipid, HBV mRNA and 3.2-kb HBV DNA were expressed in the liver by this in vivo transfection method, In the majority of rats, HBV virions and hepatitis B e antigen were found in the blood 3-7 days after transfection, after which antibody to the e antigen appeared. Two to three weeks after the transfection, glutamic-pyruvic transaminase levels were elevated in serum, hepatocyte death and lymphocyte infiltration were observed in the vicinity of the portal vein of liver, and HBV virions were no longer detected in the serum. Thus, transfection of REV into rats resulted in histological and serological changes comparable to HBV-induced acute hepatitis in humans, In contrast, no hepatocellular injury was observed in T-lymphocyte-deficient nude rats transfected with the same HBV construct, and viremia was substantially prolonged, providing direct evidence that T lymphocytes play an essential role in liver cell injury and in the clearance of HBV, This rat hepatitis model will be useful for studying pathogenesis of HBV infection.