2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/650865摘要：能有效辨識外來的入侵者是宿主成功抵禦病原的第一步，而目前對於宿主免疫系統如何辨識B型肝炎病毒、以及辨認後續如何造成病毒清除或是持續感染兩種分歧結果的詳細機制和過程仍無徹底的了解，因此這個子計畫的主要目的是利用B型肝炎病毒小鼠模式研究並解析B型肝炎病毒的病原相關分子模式(PAMP, pathogen-associated molecular pattern)與其相對應的細胞模式辨認受體(PRR, pattern recognition receptor)。此計劃提出B型肝炎病毒具有免疫激發性(immunogenic)與免疫耐受性 (immunotolerant)兩種相異類型的病原相關分子模式之假說，將分別探討B型肝炎病毒核酸核鞘、X蛋白、和其他調節性蛋白在免疫激發性病原相關分子模式中所扮演的角色，另一方面也將探討B型肝炎病毒表面抗原和表面抗原顆粒在免疫耐受性病原相關分子模式中所扮演的角色。對於宿主細胞辨識B型肝炎病毒病原相關分子模式所使用的模式辨認受體也將分別鑑定。在兩種病原相關分子模式分別與其受體結合之後續連鎖反應，包括下游訊息傳遞路徑、其如何影響後天免疫反應的產生、如何相互作用導致病毒持續感染或清除兩種不同的後果，都將仔細探究。在小鼠模式的研究成果也將在土撥鼠與人類肝臟細胞兩種自然感染的模式系統中驗證。期望能更了解B型肝炎病毒與宿主的交互作用，進而改善目前B型肝炎的治療方法。<br> Abstract: The first step of host defense to effectively defeat the pathogens is the recognition of invaders. The recognition of HBV by the cellular immune system and how it differentially leads to viral clearance or persistence have not been elucidated clearly. In this sub-project, we aim to clarify the pathogen-associated molecular patterns (PAMPs) of HBV and their corresponding pattern recognition receptors (PRRs) by the hydrodynamics-base mouse model. Two functionally opposite categories of PAMPs of HBV are hypothesized: immunogenic and immunotolerant. The immunogenic roles of HBV nucleocapsid as well as HBx and other viral regulators will be investigated. On the other hand, the immunotolerant role of HBsAg or HBsAg particles will be explored. Furthermore, we will identify the cellular receptors recognizing these PAMPs and examine their downstream signaling pathways, transition to adaptive immunity and how they collectively determine viral persistence/clearance.The findings from the HBV mouse model will be further validated in the nature infection models, including the woodchuck hepatitis virus (WHV) infection in the woodchuck model and HBV infection in human primary hepatocytes. Our research results will eventually provide a better understanding of HBV-host interaction, which would be helpful to improve current treatment of HBV infection.B型肝炎病毒B型肝炎病毒核心抗原病原相關分子模式細胞模式辨認受體高壓流體注射轉染先天性免疫反應