Woollard David J, Haqshenas Gholamreza, Dong Xuebin, Pratt Bridget F, Kent Stephen J, Gowans Eric J
The Burnet Institute, G.P.O. Box 2284, Melbourne, Victoria, Australia.
J Virol. 2008 Mar;82(6):3054-60. doi: 10.1128/JVI.01153-07. Epub 2007 Dec 19.
GB virus B (GBV-B) is a hepatotropic virus that is closely related to hepatitis C virus (HCV). GBV-B causes acute hepatitis in infected marmosets and tamarins and is therefore a useful small-animal model for the study of HCV. We investigated virus-specific T-cell responses in marmosets infected with GBV-B. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay responses in the peripheral blood of two marmosets were assessed throughout the course of GBV-B infection. These T-cell responses were directed against the GBV-B nonstructural proteins 3 (NS3), 4A (NS4A), and 5B (NS5B), and their appearance was temporally associated with clearance of viremia. These marmosets were then rechallenged with GBV-B at least 3 months after clearance of the primary infection to determine if the animals were protected from reinfection. There was no detectable viremia following reinfection, although a sharp increase in T-cell responses against GBV-B proteins was observed. Epitope mapping of T-cell responses to GBV-B was performed with liver and blood samples from both marmosets after rechallenge with GBV-B. Three shared, immunodominant T-cell epitopes within NS3 were identified in animals with multiple common major histocompatibility complex class I alleles. IFN-gamma ELISPOT responses were also detected in the livers of two marmosets that had resolved a primary GBV-B infection. These responses were high in frequency and were directed against epitopes within GBV-B NS3, NS4A, and NS5B proteins. These results indicate that virus-specific T-cell responses are detectable in the liver and blood of GBV-B-infected marmosets and that the clearance of GBV-B is associated with the appearance of these responses.
GB病毒B（GBV-B）是一种嗜肝病毒，与丙型肝炎病毒（HCV）密切相关。GBV-B可在感染的狨猴和绢毛猴中引起急性肝炎，因此是研究HCV的一种有用的小动物模型。我们研究了感染GBV-B的狨猴体内病毒特异性T细胞反应。在GBV-B感染的整个过程中，评估了两只狨猴外周血中的γ干扰素（IFN-γ）酶联免疫斑点（ELISPOT）分析反应。这些T细胞反应针对GBV-B非结构蛋白3（NS3）、4A（NS4A）和5B（NS5B），它们的出现与病毒血症的清除在时间上相关。然后在初次感染清除后至少3个月，用GBV-B对这些狨猴进行再次攻击，以确定动物是否受到保护而免于再次感染。再次感染后未检测到病毒血症，尽管观察到针对GBV-B蛋白的T细胞反应急剧增加。在用GBV-B再次攻击后，对两只狨猴的肝脏和血液样本进行了T细胞对GBV-B反应的表位作图。在具有多个共同主要组织相容性复合体I类等位基因的动物中，在NS3内鉴定出三个共享的免疫显性T细胞表位。在两只已解决原发性GBV-B感染的狨猴的肝脏中也检测到IFN-γ ELISPOT反应。这些反应频率很高，针对GBV-B NS3、NS4A和NS5B蛋白内的表位。这些结果表明，在感染GBV-B的狨猴的肝脏和血液中可检测到病毒特异性T细胞反应，并且GBV-B的清除与这些反应的出现相关。
