在小鼠動物模式中探討B型肝炎病毒核心蛋白所引發的先天性免疫反應

Induction of innate immunity by HBV core protein in mouse animal model

薛穎超(Ying-Chao Hsueh)

指導教授 ： 許秉寧

國立臺灣大學/醫學院/免疫學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.02137

摘要

無資料

關鍵字

B型肝炎病毒 ； 核心蛋白 ； 先天性免疫 ； 腫瘤壞死因子-α ； 脾臟酪胺酸激酶庫氏細胞

並列摘要

Chronic hepatitis B infection (HBV) is closely correlated to elevated risks of liver cirrhosis and hepatocellular carcinoma. However, the underlying mechanisms leading to viral persistency are not fully understood. Among the viral factors, HBV core protein has been identified being critical for HBV persistence. On the other hand, type I interferons and TNF-α are host factors required for HBV clearance. Hence, we hypothesize that the HBV mutants might evade essential innate immune responses which lead to its persistence in human host. Using reporter assay in the hydrodynamic injection mouse model, we found that WT HBV could induce higher IFN-β promoter activity than persistent HBc mutants. The Kupffer cells also expressed more pro-inflammatory cytokine genes in response to WT HBV. As the HBV mutants harboring structural changes in the HBV core region might lead to variable outcomes of innate immune response, we then characterized the stimulatory effect of recombinant HBc in vitro with macrophage and dendritic cell line. HBc could stimulate DC to secrete TNF-α through a calcium-dependent and Syk-dependent manner in which the HBc capsid structure was also required. Furthermore, the role of Kupffer cells in viral clearance was assayed by clodronate-liposome treatment to deplete Kupffer cells in mice treated with HBV hydrodynamic injection; however, HBV was still cleared in the absence of Kupffer cells. Our study indicated that HBc had a stimulatory effect on antigen-presenting cells which leaded to the induction of innate immunity.

並列關鍵字

hepatitis B virus ； HBc ； innate immunity ； TNF-α ； Syk ； Kupffer cell

參考文獻

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