Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, 10065, USA.
Virology. 2024 Dec;600:110265. doi: 10.1016/j.virol.2024.110265. Epub 2024 Oct 18.
Primary human hepatocyte (PHH) models have limited longevity and require high inoculum for HBV infection with minimal spread. We aimed to develop 3D cell culture models to overcome the limitations of existing models and to expand their utility for drug-related studies. Here, we report the establishment of two spheroid models utilizing de novo HBV-infected mouse-passaged (mp)PHH and mpPHH isolated from HBV-infected liver chimeric mice (HBV-mpPHH). Our data demonstrates that our models maintain detectable infection and human albumin levels up to 75 days, and therefore have enhanced longevity compared to existing models. As a proof-of-concept we used our de novo HBV-infected model as a drug-testing platform to validate an HBV capsid assembly modulator (CpAM). We report that we have established two HBV-infected 3D cell culture models and have characterized these models as practical and novel approaches with the potential to enhance the relevance and scope of in vitro HBV studies.
原代人肝细胞 (PHH) 模型的寿命有限，需要高接种量才能感染 HBV，并且传播范围有限。我们旨在开发 3D 细胞培养模型，以克服现有模型的局限性，并扩大其在药物相关研究中的应用。在这里，我们报告了两种利用从头开始感染 HBV 的小鼠传代 (mp)PHH 和从 HBV 感染的嵌合小鼠肝脏中分离的 mpPHH 建立的球体模型。我们的数据表明，我们的模型可以保持可检测的感染和人白蛋白水平长达 75 天，因此与现有模型相比具有更长的寿命。作为概念验证，我们使用我们的从头开始感染的模型作为药物测试平台来验证 HBV 衣壳组装调节剂 (CpAM)。我们报告说，我们已经建立了两种 HBV 感染的 3D 细胞培养模型，并将这些模型描述为实用且新颖的方法，具有提高体外 HBV 研究相关性和范围的潜力。
