Hepatitis D Virus induced pathogenesis and interaction with the immune system (A08)

丁型肝炎病毒感染显示最严重的临床过程，但没有直接的抗病毒治疗。我们希望采用HDV感染的动物模型（人肝嵌合小鼠）并开发新的免疫活性模型（人源化NTCP小鼠）来研究病毒-宿主相互作用（先天性和适应性免疫反应），这些相互作用可能是导致HDV相关肝损伤和患者中观察到的严重临床过程的原因。此外，我们希望通过分析体内逃避机制和通过从干扰素抗性和敏感HDV株产生嵌合病毒来阐明特定HDV株对干扰素-α治疗无应答的机制。所获得的知识将有助于开发新的抗病毒策略。

Hepatitis D Virus infection shows the most severe clinical course, however no direct antiviral treatment is available. We want to employ animal models of HDV infection (human liver chimeric mice) and develop new immunocompetent models (humanized NTCP mice) to investigate virus-host interactions (innate and adaptive immune responses) that may be responsible for HDV-associated liver injury and the severe clinical course observed in patients. Furthermore, we want to elucidate the mechanisms accountable for the non-response of specific HDV strains to interferon-alpha therapy by analyzing evasion mechanisms in vivo and by generating mosaic viruses from interferon-resistant and -sensible HDV strains. Knowledge obtained shall contribute to the development of new antiviral strategies.