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首页> 外文期刊>Archives of virology >Woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis B?
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Woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis B?

机译:免疫优势抗原决定簇刺激的土拨鼠肝炎病毒核心基因缺失和外周血单核细胞的增殖反应:在慢性乙型肝炎的土拨鼠模型中病毒免疫逃逸?

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摘要

Marmota monax and its natural infection by woodchuck hepatitis virus (WHV) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the presence of viral variants in the core gene of chronically WHV-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (PBMCs') responses after stimulation with a specific WHV core peptide. Sequences' analysis of the WHV core region from eight WHV chronically infected woodchucks have been performed after in vitro stimulation with an immunodominant epitope of the WHV core protein (amino acids [aa] 96-110). Following this stimulation, positive PBMC responses at each point of follow-up were observed for four animals (group A), and weak immune responses at one or a few points of follow-up were observed for the remaining four animals (group B). The WHV core gene sequences contained amino acid deletions (aa 84-126, aa 84-113) in three of four group A animals and in none of group B animals. In the group A animals, the same deletions were observed in liver specimens and in two of four tumor specimens. Hepatocellular carcinoma (HCC) was diagnosed in all group A animals and in one group B animal. In conclusion, internal deletions in the core region correlated with a sustained PBMC response to the immunogenic peptide (96-110) of the core protein. A possible role of this relationship in hepatocarcinogenesis could be hypothesized; however, this needs to be investigated in patients with chronic HBV infection. The evaluation of virus-specific T-cell responses and T-cell epitopes that are possibly related to the mechanisms of viral evasion should be further investigated in order to design combined antiviral and immune approaches to control chronic HBV infection.
机译:早獭早獭及其由土拨鼠肝炎病毒(WHV)引起的自然感染可以用作评估慢性乙型肝炎病毒(HBV)感染期间病毒持久性机制的预测模型。这项研究的目的是调查在慢性WHV感染的土拨鼠的核心基因中存在病毒变异体,该变异体在用特定的WHV核心肽刺激后显示出两种不同的外周血单核细胞(PBMCs)反应模式。在体外用WHV核心蛋白(氨基酸[aa] 96-110)的免疫表位刺激后,对八只WHV慢性感染的土拨鼠的WHV核心区域进行了序列分析。在这种刺激之后,对于四只动物(A组)在每个随访点观察到阳性PBMC应答,而对于其余四只动物(B组)在一个或几个随访点观察到弱免疫应答。 WHV核心基因序列在四只A组动物中的三只中没有氨基酸缺失(aa 84-126,aa 84-113)。在A组动物中,在肝脏标本和四个肿瘤标本中的两个中观察到相同的缺失。在所有A组动物和B组动物中均诊断出肝细胞癌(HCC)。总之,核心区域的内部缺失与对核心蛋白免疫原性肽(96-110)的持续PBMC反应有关。可以推测这种关系在肝癌发生中的可能作用;但是,这需要对患有慢性HBV感染的患者进行调查。为了设计结合抗病毒和免疫方法来控制慢性HBV感染,应进一步研究对可能与病毒逃逸机制有关的病毒特异性T细胞应答和T细胞表位的评估。

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