Charles River Laboratories, 2333 CR Leiden, The Netherlands.
OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Cells. 2023 Apr 12;12(8):1138. doi: 10.3390/cells12081138.
Enteroviruses are a leading cause of upper respiratory tract, gastrointestinal, and neurological infections. Management of enterovirus-related diseases has been hindered by the lack of specific antiviral treatment. The pre-clinical and clinical development of such antivirals has been challenging, calling for novel model systems and strategies to identify suitable pre-clinical candidates. Organoids represent a new and outstanding opportunity to test antiviral agents in a more physiologically relevant system. However, dedicated studies addressing the validation and direct comparison of organoids versus commonly used cell lines are lacking. Here, we described the use of human small intestinal organoids (HIOs) as a model to study antiviral treatment against human enterovirus 71 (EV-A71) infection and compared this model to EV-A71-infected RD cells. We used reference antiviral compounds such as enviroxime, rupintrivir, and 2'--methylcytidine (2'CMC) to assess their effects on cell viability, virus-induced cytopathic effect, and viral RNA yield in EV-A71-infected HIOs and cell line. The results indicated a difference in the activity of the tested compounds between the two models, with HIOs being more sensitive to infection and drug treatment. In conclusion, the outcome reveals the value added by using the organoid model in virus and antiviral studies.
肠道病毒是上呼吸道、胃肠道和神经系统感染的主要原因。由于缺乏特定的抗病毒治疗，肠道病毒相关疾病的治疗受到阻碍。此类抗病毒药物的临床前和临床开发具有挑战性，需要新型模型系统和策略来确定合适的临床前候选药物。类器官代表了在更接近生理的系统中测试抗病毒药物的新的和杰出的机会。然而，缺乏专门针对验证和直接比较类器官与常用细胞系的研究。在这里，我们描述了使用人小肠类器官（HIOs）作为模型来研究针对人类肠道病毒 71（EV-A71）感染的抗病毒治疗，并将该模型与 EV-A71 感染的 RD 细胞进行了比较。我们使用了参考抗病毒化合物，如 enviroxime、rupintrivir 和 2'-甲基胞苷（2'CMC），以评估它们对 EV-A71 感染的 HIO 和细胞系中细胞活力、病毒诱导的细胞病变效应和病毒 RNA 产量的影响。结果表明，两种模型中测试化合物的活性存在差异，HIO 对感染和药物治疗更敏感。总之，该结果揭示了在病毒和抗病毒研究中使用类器官模型的附加值。
