. doi: 10.1016/j.virs.2026.09.011
Citation: Jiajing Li, Marieke Alzeer, Xin Wang, Amber Hof, Debbie L.C. van den Berg, Qiuwei Pan. Human brain organoids and neural progenitor cells model oropouche virus infection and reveal varied responses to antiviral therapies .VIROLOGICA SINICA, 2026, 41(5) : 1256-1260.  http://dx.doi.org/10.1016/j.virs.2026.09.011

人脑类器官与神经前体细胞用于构建奥罗普切病毒感染模型,并揭示其对抗病毒疗法的差异化应答

  • 奥罗普切病毒(Oropouche virus,OROV)近年来再度引发疫情,并伴随神经系统并发症及垂直传播相关不良妊娠结局,但其神经嗜性以及相关抗病毒治疗仍缺乏充分研究。本研究采用诱导多能干细胞来源的皮层脑类器官(cortical brain organoids,CBOs)和神经祖细胞(neural progenitor cells,NPCs)建立OROV体外神经感染模型,同时评估N4-羟基胞苷(N4-hydroxycytidine,NHC)及干扰素α(interferon-α,IFN-α)的抗病毒作用。结果显示,OROV可在CBOs和NPCs中有效复制,并感染不同神经分化阶段的细胞,同时引起细胞损伤及类器官结构紊乱。NHC作为莫努匹韦的活性形式,在神经模型中仅表现出有限的抗OROV活性;IFN-α可显著抑制NPCs中的OROV感染,但在脑类器官中的抗病毒作用较弱。二维和三维模型间观察到的药物反应差异进一步表明,脑类器官可为OROV抗病毒药物评价提供重要补充,并有助于更全面地评估候选治疗策略。

Human brain organoids and neural progenitor cells model oropouche virus infection and reveal varied responses to antiviral therapies

  • Highlights
    1 Human brain organoids and neural progenitor cells are susceptible to OROV infection.
    2 NHC (the active form of molnupiravir) shows suboptimal antiviral efficacy against OROV in neural models.
    3 IFN-α strongly inhibits OROV in NPCs but shows limited antiviral potency in brain organoids.
    4 Discrepancies between 2D and 3D platforms highlight the indispensable role of organoids in antiviral drug discovery.

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    Human brain organoids and neural progenitor cells model oropouche virus infection and reveal varied responses to antiviral therapies

      Corresponding author: Debbie L.C. van den Berg, d.vandenberg@erasmusmc.nl
      Corresponding author: Qiuwei Pan, q.pan@erasmusmc.nl
    • a. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, 3015 GD, the Netherlands;
    • b. Department of Developmental Biology, Erasmus MC-University Medical Center, Rotterdam, 3015 GD, the Netherlands

    Abstract: Highlights
    1 Human brain organoids and neural progenitor cells are susceptible to OROV infection.
    2 NHC (the active form of molnupiravir) shows suboptimal antiviral efficacy against OROV in neural models.
    3 IFN-α strongly inhibits OROV in NPCs but shows limited antiviral potency in brain organoids.
    4 Discrepancies between 2D and 3D platforms highlight the indispensable role of organoids in antiviral drug discovery.

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