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迈向丙型肝炎病毒替代模型:GB病毒B型肝炎病原体的感染性分子克隆。

Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent.

作者信息

Bukh J, Apgar C L, Yanagi M

机构信息

Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892-0740, USA.

出版信息

Virology. 1999 Sep 30;262(2):470-8. doi: 10.1006/viro.1999.9941.

DOI:10.1006/viro.1999.9941
PMID:10502525
Abstract

GB virus-B (GBV-B) is a member of the Flaviviridae family of viruses. This RNA virus infects tamarins, but its natural host is not known. GBV-B has special interest because it is the virus that is most closely related to hepatitis C virus (HCV), an important human pathogen. In the present study, we identified a previously unrecognized sequence at the 3' end of the GBV-B genome. This new 3' terminal sequence can form several predicted stem-loop structures as is typical for other members of the Flaviviridae family. We constructed molecular clones and showed that the new 3' UTR sequence was critical for in vivo infectivity. After intrahepatic transfection of two tamarins with RNA transcripts of the full-length GBV-B clone, we detected high viral titers from Week 1 postinoculation with peak titers of approximately 10(8) genome equivalents/ml. The viremic pattern of GBV-B infection in the transfected animals was the same as in animals inoculated intravenously with the virus pool used as the cloning source. The sequence of the recombinant virus was recovered from one of the tamarins and shown to be identical to that of the infectious clone. The development of severe hepatitis in both tamarins infected with the recombinant GBV-B virus provides formal proof that GBV-B is a true hepatitis virus.

摘要

GB病毒B(GBV-B)是黄病毒科病毒的成员。这种RNA病毒感染绢毛猴,但它的天然宿主尚不清楚。GBV-B备受关注,因为它是与丙型肝炎病毒(HCV,一种重要的人类病原体)关系最为密切的病毒。在本研究中,我们在GBV-B基因组的3'端鉴定出一个先前未被识别的序列。这个新的3'末端序列可以形成几个预测的茎环结构,这是黄病毒科其他成员的典型特征。我们构建了分子克隆,并表明新的3'非翻译区序列对体内感染性至关重要。在用全长GBV-B克隆的RNA转录本对两只绢毛猴进行肝内转染后,我们在接种后第1周检测到高病毒滴度,峰值滴度约为10(8)基因组当量/毫升。转染动物中GBV-B感染的病毒血症模式与静脉接种用作克隆源的病毒库的动物相同。从其中一只绢毛猴中回收了重组病毒的序列,并显示与感染性克隆的序列相同。感染重组GBV-B病毒的两只绢毛猴均发生严重肝炎,这提供了GBV-B是一种真正的肝炎病毒的正式证据。

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Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent.迈向丙型肝炎病毒替代模型:GB病毒B型肝炎病原体的感染性分子克隆。
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