Gastrointestinal organoids in the study of viral infections.
Gastrointestinal organoids in the study of viral infections.
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病毒感染研究中的胃肠道类器官。
DOI：
10.1152/ajpgi.00152.2022
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hyser,JosephM
中科院分区：
文献类型：
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作者：
Gebert,JThomas;Scribano,Francesca;Engevik,KristenA;Perry,JacobL;Hyser,JosephM
病毒是最普遍的肠道病原体之一。虽然病毒学家在历史上依赖于细胞系和动物模型，但人类肠道类器官（HIO）继续受到欢迎。HIO是维持肠上皮细胞类型多样性的非转化、干细胞衍生的离体细胞培养物。它们提供比标准动物模型更高的通量，同时比转化细胞系更准确地模拟感染的天然组织。在这里，我们回顾了最近的文献，突出了由HIO促进的病毒学进展。我们讨论了HIOs的变化和局限性，HIOs如何允许培养以前无法培养的病毒，以及它们如何提供对向性，进入，复制动力学和宿主-病原体相互作用的见解。在每种情况下，我们讨论典型的病毒和原型研究。我们讨论了如何的速度和灵活性的HIO为基础的研究有助于我们的知识SARS-CoV-2和抗病毒治疗。最后，我们讨论了目前的局限性和未来的发展方向，以克服这些。
Viruses are among the most prevalent enteric pathogens. Although virologists historically relied on cell lines and animal models, human intestinal organoids (HIOs) continue to grow in popularity. HIOs are nontransformed, stem cell-derived, ex vivo cell cultures that maintain the cell type diversity of the intestinal epithelium. They offer higher throughput than standard animal models while more accurately mimicking the native tissue of infection than transformed cell lines. Here, we review recent literature that highlights virological advances facilitated by HIOs. We discuss the variations and limitations of HIOs, how HIOs have allowed for the cultivation of previously uncultivatable viruses, and how they have offered insight into tropism, entry, replication kinetics, and host-pathogen interactions. In each case, we discuss exemplary viruses and archetypal studies. We discuss how the speed and flexibility of HIO-based studies contributed to our knowledge of SARS-CoV-2 and antiviral therapeutics. Finally, we discuss the current limitations of HIOs and future directions to overcome these.