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在人源化小鼠中模拟肝炎病毒感染和治疗策略。

Modeling hepatitis virus infections and treatment strategies in humanized mice.

机构信息

INSERM U1135, Paris, France; Université Pierre et Marie Curie, Paris, France.

Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France; INSERM U1223, 75724 Paris, France.

出版信息

Curr Opin Virol. 2017 Aug;25:119-125. doi: 10.1016/j.coviro.2017.07.029. Epub 2017 Aug 31.

Abstract

Hepatitis viruses cause chronic liver diseases such as fibrosis, cirrhosis and hepatocellular carcinomas that are difficult to treat and constitute a global health problem. Species-specific viral tropism has limited the usefulness of small animal models to study the impact of viral hepatitis. Immunodeficient mice grafted with human hepatocytes are susceptible to hepatitis viruses B, C, D and E (HBV, HCV, HDV and HEV), developing full viral life cycles, and delivering a means to investigate virus-host interactions and antiviral treatments. These chimeric humanized mouse models have been further grafted with humanized immune systems to decipher immune responses following hepatotropic viral infections, the ensuing pathophysiology, and to test novel therapeutic strategies.

摘要

肝炎病毒可引起慢性肝脏疾病,如纤维化、肝硬化和肝细胞癌,这些疾病难以治疗,是一个全球性的健康问题。病毒的物种特异性嗜性限制了小动物模型在研究病毒性肝炎影响方面的作用。免疫缺陷小鼠移植人肝细胞后易感染乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)、丁型肝炎病毒(HDV)和戊型肝炎病毒(HEV),可完成完整的病毒生命周期,为研究病毒-宿主相互作用和抗病毒治疗提供了手段。这些嵌合的人源化小鼠模型进一步移植了人源化免疫系统,以解析嗜肝病毒感染后的免疫反应、随后的病理生理学,并测试新的治疗策略。

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