CONCISE REVIEW IN MECHANISMS OF DISEASE A Critical Role for the Chimpanzee Model in the Study of Hepatitis C
CONCISE REVIEW IN MECHANISMS OF DISEASE A Critical Role for the Chimpanzee Model in the Study of Hepatitis C
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发表时间：
2004
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通讯作者：
J. Bukh
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作者：
J. Bukh
黑猩猩仍然是研究丙型肝炎病毒(HCV)的唯一公认的动物模型。在黑猩猩身上进行的研究在发现丙型肝炎病毒方面发挥了关键作用，并将继续在确定这一重要人类病原体的自然历史方面发挥重要作用。在没有可复制的细胞培养系统的情况下，丙型肝炎病毒攻击池的传染性滴度只能在黑猩猩身上确定。最近对黑猩猩的研究为宿主免疫反应的性质提供了新的见解--特别是肝内反应--在初次和继发性实验性丙型肝炎感染后。丙型肝炎病毒候选疫苗的免疫原性和有效性只能在黑猩猩身上进行测试。最后，如果没有黑猩猩，就不可能证明丙型肝炎病毒感染性克隆的传染性。当来自分子克隆的RNA转录物直接接种到肝脏中时，黑猩猩就会被感染。这种转基因产生的感染与静脉感染野生型丙型肝炎病毒的动物没有显著差异。接种到黑猩猩体内的RNA来自单一序列，因此这些动物感染了单克隆性丙型肝炎病毒。单克隆性感染简化了对丙型肝炎病毒的研究，因为病毒与宿主的相互作用不会被自然感染中总是存在的准种所混淆。此外，它还允许在保护性免疫研究和测试候选疫苗的效力方面进行真正的同源挑战。最后，这一体内转移系统使首次测试遗传因素对丙型肝炎病毒传染性的重要性成为可能。(《肝病》2004；39：1469-1475。)
Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV). Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees. Recent studies in chimpanzees have provided new insight into the nature of host immune responses—particularly the intrahepatic responses—following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. The RNA inoculated into chimpanzees originated from a single sequence, and the animals therefore had a monoclonal HCV infection. Monoclonal infection simplifies studies of HCV, because virus interaction with the host is not confounded by the quasispecies invariably present in a natural infection. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates. Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity. (HEPATOLOGY 2004;39: 1469–1475.)