评估乙型肝炎病毒感染和宿主细胞间反应,使用肝脏内胆管细胞器官
Chuan K Lim1,2,3, Ornella Romeo3, Bang M Tran2
1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Journal of medical virology
|November 27, 2023
概括
人体肝脏内胆固醇细胞器官 (ICO) 支持乙型肝炎病毒 (HBV) 感染和复制. 捐赠者变异影响病毒动态和药物反应,为个性化抗病毒测试铺平了道路.
科学领域:
- 肝病学和病毒学.
- 有机物技术 有机物技术
- 传染病建模 传染病建模
背景情况:
- 乙型肝炎病毒 (HBV) 感染仍然是一个重大的全球健康挑战.
- 准确的模型对于理解HBV病变和开发有效治疗方法至关重要.
- 肝脏内胆固醇细胞器官 (ICO) 为研究肝脏疾病提供了一个有前途的体外系统.
研究的目的:
- 评估肝脏内胆固醇细胞器官 (ICO) 作为乙型肝炎病毒 (HBV) 感染的模型.
- 在ICO模型中评估病毒复制,细胞反应和药物疗效的宿主差异.
- 探索ICO在个性化抗病毒药物测试方面的潜力.
主要方法:
- 从人类肝脏样本生成和区分12个ICO.
- ICO结构和HBV入口受体表达的表征.
- 优化HBV感染 (基因型B,C和D) 的培养条件,并评估病毒标记物 (RNA,ccDNA,HBsAg,HBeAg) 和细胞反应 (ISG).
主要成果:
- 区分良好的ICO支持HBV感染和复制,病毒载荷和动态的变化取决于捐赠者.
- 对抗病毒和免疫调节剂的药物反应在ICO捐赠者之间差异很大.
- 尽管干扰素刺激基因 (ISG) 对外部刺激的反应强大,但在ICO模型中,HBV感染并没有提高ISG的调节.
结论:
- 人体ICO作为研究HBV感染和复制的可行模型.
- 观察到的依赖于捐赠者的变化突显了个性化药物查的潜力.
- ICO可用于开发针对HBV抗病毒药物的个性化药物测试平台.
相关概念视频
01:25Hepatitis
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
01:28Viral Hepatitis I: Introduction
Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...