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. 2020 Jul 6;14(7):e0008413. doi: 10.1371/journal.pntd.0008413. eCollection 2020 Jul.
Global Zika virus (ZIKV) outbreaks and their link to microcephaly have raised major public health concerns. However, the mechanism of maternal-fetal transmission remains largely unknown. In this study, we determined the role of yolk sac (YS) microglial progenitors in a mouse model of ZIKV vertical transmission. We found that embryonic (E) days 6.5-E8.5 were a critical window for ZIKV infection that resulted in fetal demise and microcephaly, and YS microglial progenitors were susceptible to ZIKV infection. Ablation of YS microglial progenitors significantly reduced the viral load in both the YS and the embryonic brain. Taken together, these results support the hypothesis that YS microglial progenitors serve as "Trojan horses," contributing to ZIKV fetal brain dissemination and congenital brain defects.
全球 Zika 病毒(ZIKV)爆发及其与小头症的关联引起了重大公共卫生关注。然而,母婴传播的机制在很大程度上仍不清楚。在这项研究中,我们确定了卵黄囊(YS)小胶质前体细胞在 ZIKV 垂直传播的小鼠模型中的作用。我们发现,胚胎(E)第 6.5 天至第 8.5 天是 ZIKV 感染导致胎儿死亡和小头症的关键窗口,并且 YS 小胶质前体细胞易受 ZIKV 感染。YS 小胶质前体细胞的消融显著降低了 YS 和胚胎大脑中的病毒载量。总之,这些结果支持了 YS 小胶质前体细胞作为“特洛伊木马”的假说,有助于 ZIKV 胎儿大脑传播和先天性脑缺陷。