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一个新的体外系统,用于同时感染乙型肝炎,C型肝炎,D型肝炎和E型肝炎病毒

Roxanne Fouillé¹, Eloi R Verrier², Amse De Meyer³

¹CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.

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概括

一个新的体外模型允许同时感染乙型肝炎,D型肝炎,C型肝炎和E型肝炎病毒. 该模型确定了Farnesoid X受体 (FXR) 激动剂作为治疗多种肝炎感染的潜在广泛抗病毒药物.

科学领域:

肝病学肝病学是一种肝病学.
病毒学病毒学
药物发现药物发现药物发现

背景情况:

肝炎病毒 (HBV,HDV,HCV,HEV) 导致慢性肝病.
缺乏用于多种感染的体外模型限制了对病毒相互作用和抗病毒交叉反应性的理解.
对于慢性肝炎感染,治疗选择有限.

研究的目的:

建立第一个用于同时感染HBV,HDV,HCV和HEV的体外模型.
在多个感染细胞中研究病毒相互作用和抗病毒功效.
为广泛的肝炎治疗确定新的治疗点.

主要方法:

开发了一个差异化的HuH7.5-NTCP细胞培养模型 (dHuH7.5-NTCP).
单个或多个肝炎病毒感染的细胞.
用已知的抗病毒药物和法尔内索伊德X受体 (FXR) 激动剂治疗感染细胞.
在感染HEV的HuHep小鼠中验证的发现.

主要成果:

该dHuH7.5-NTCP模型支持HBV,HDV,HCV和HEV的复制超过4周.
确认了索福斯布维尔 (HCV,HEV) 和IFN-α (HCV,HEV,HDV) 的抗病毒作用.
确定了GW4064 (FXR激动剂) 作为HEV复制的强有力的抑制剂,在体内观察到与vonafexor相似的效果.

结论:

建立了第一个用于所有四种主要肝炎病毒的多种感染的体外模型.
证明了FXR激动剂对多种肝炎病毒的广泛抗病毒潜力.
为开发针对病毒治愈的新疗法策略铺平了道路.

关键词:

乙型肝炎病毒的感染.肝炎C病毒感染者肝炎D病毒感染者肝炎E病毒感染者广泛作用的抗病毒药物.药物查对药物进行查.肝细胞肝细胞肝细胞

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