Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent
Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent
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DOI：
10.1006/viro.1999.9941
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发表时间：
1999-09-30
期刊：
影响因子：
3.7
通讯作者：
Yanagi, M
中科院分区：
文献类型：
--
作者：
Bukh, J;Apgar, CL;Yanagi, M
GB病毒-B（GBV-B）是黄病毒科病毒家族的成员。这种RNA病毒感染绢毛猴，但其天然宿主尚不清楚。GBV-B具有特殊的意义，因为它是与丙型肝炎病毒（HCV）（一种重要的人类病原体）最密切相关的病毒。在本研究中，我们在GBV-B基因组的3'端鉴定了一个以前未被识别的序列。这种新的3'末端序列可以产生几种预测的茎环结构，这对于黄病毒科的其他成员是典型的。我们构建了分子克隆，并表明新的3' UTR序列是体内感染性的关键。用全长GBV-B克隆的RNA转录物肝内转染两种绢毛猴后，我们从接种后第1周检测到高病毒滴度，峰值滴度接近10（8）基因组当量/ml。转染动物中GBV-B感染的病毒血模式与静脉接种用作克隆源的病毒库的动物相同。重组病毒的序列从一只绢毛猴中回收，并显示与感染性克隆的序列相同。在感染重组GBV-B病毒的两种绢毛猴中严重肝炎的发展提供了GBV-B是真正的肝炎病毒的正式证据。(C)北京：科学出版社.
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 farm 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 similar to 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. (C) 1999 Academic Press.