Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, Texas, United States of America.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS Negl Trop Dis. 2021 Mar 3;15(3):e0009183. doi: 10.1371/journal.pntd.0009183. eCollection 2021 Mar.
Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology.
全球寨卡病毒（ZIKV）爆发及其与小头症的强烈关联引起了重大公共卫生关注。寨卡病毒已被报道影响神经干细胞/祖细胞（NS/PCs）中的固有免疫反应。然而，这些免疫因素如何影响神经发生尚不清楚。在这项研究中，我们使用源自亚洲裔美国人谱系的寨卡病毒株 PRVABC59 感染最初源自胎儿大脑的原代人 NS/PCs。我们发现寨卡病毒过度激活固有免疫途径中的关键分子，以细胞阶段依赖性方式损害神经发生。抑制过度激活的固有免疫反应可改善寨卡病毒诱导的神经发生减少。因此，这项研究表明，寨卡病毒感染后协调 NS/PCs 中的宿主固有免疫反应可能是减轻寨卡病毒相关神经病理学的有前途的治疗方法。
Zotero 插件
