Role of microglia in the dissemination of Zika virus from mother to fetal brain.
Pei XuChao ShanTiffany J DunnXuping XieHongjie XiaJunling GaoJavier Allende LabastidaJing ZouPaula P VillarrealCaitlin R SchlagalYongjia YuGracie VargasShannan L RossiNikolaos VasilakisPei-Yong ShiScott C WeaverPing WuPublished in: PLoS neglected tropical diseases (2020)
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.
Keyphrases
- zika virus
- dengue virus
- inflammatory response
- resting state
- white matter
- public health
- neuropathic pain
- aedes aegypti
- lipopolysaccharide induced
- lps induced
- mouse model
- functional connectivity
- cerebral ischemia
- spinal cord
- multiple sclerosis
- atrial fibrillation
- body mass index
- physical activity
- preterm birth
- global health