Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, New York 10065.
Cold Spring Harb Perspect Med. 2019 Mar 1;9(3):a031799. doi: 10.1101/cshperspect.a031799.
Similar to other hepatotropic viruses, hepatitis E virus (HEV) has been notoriously difficult to propagate in cell culture, limiting studies to unravel its biology. Recently, major advances have been made by passaging primary HEV isolates and selecting variants that replicate efficiently in carcinoma cells. These adaptations, however, can alter HEV biology. We have explored human embryonic or induced pluripotent stem cell (hESC/iPSC)-derived hepatocyte-like cells (HLCs) as an alternative to conventional hepatoma and hepatocyte cell culture systems for HEV studies. HLCs are permissive for nonadapted HEV isolate genotypes (gt)1-4 replication and can be readily genetically manipulated. HLCs, therefore, enable studies of pan-genotype HEV biology and will serve as a platform for testing anti-HEV treatments. Finally, we discuss how hepatocyte polarity is likely an important factor in the maturation and spread of infectious HEV particles.
类似于其他嗜肝病毒，戊型肝炎病毒 (HEV) 一直难以在细胞培养中繁殖，这限制了对其生物学的研究。最近，通过传代原发性 HEV 分离株和选择在癌细胞中高效复制的变体，在这方面取得了重大进展。然而，这些适应会改变 HEV 的生物学特性。我们已经探索了人胚胎或诱导多能干细胞 (hESC/iPSC) 衍生的肝细胞样细胞 (HLC)，作为替代传统肝癌和肝细胞培养系统用于 HEV 研究的方法。HLC 允许未经适应的 HEV 分离株基因型 (gt)1-4 复制，并且可以容易地进行遗传操作。因此，HLC 能够研究 pan-genotype HEV 生物学，并将作为测试抗 HEV 治疗的平台。最后，我们讨论了肝细胞极性如何可能是成熟和传播感染性 HEV 颗粒的重要因素。
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