Abstract
Zika virus (ZIKV) is a flavivirus that is highly neurotropic causing congenital abnormalities and neurological damage to the central nervous systems (CNS). In this study, we used a human induced pluripotent stem cell (iPSC)-derived blood brain barrier (BBB) model to demonstrate that ZIKV can infect brain endothelial cells (i-BECs) without compromising the BBB barrier integrity or permeability. Although no disruption to the BBB was observed post-infection, ZIKV particles were released on the abluminal side of the BBB model and infected underlying iPSC-derived neural progenitor cells (i-NPs). AXL, a putative ZIKV cellular entry receptor, was also highly expressed in ZIKV-susceptible i-BEC and i-NPs. This iPSC-derived BBB model can help elucidate the mechanism by which ZIKV can infect BECs, cross the BBB and gain access to the CNS.
Highlights
Zika virus (ZIKV), a mosquito-borne flavivirus, was generally perceived to cause mild infections in adults
We have described [18] a human blood– brain barrier (BBB) model based on a two-step differentiation protocol of induced pluripotent stem cells derived from amniotic fluid cells into induced brain endothelial cells (i-BECs), as well as into neural progenitor cells (i-NPs) and mature neurons (i-Ns) (Additional file 1: Figure S1)
ZIKV-infected i-BEC monolayers remained viable with no visible compromise to the integrity and continuity of their intercellular contacts, as assessed by their staining for a tight junction protein, ZO-1 (Fig. 2b)
Summary
Zika virus (ZIKV), a mosquito-borne flavivirus, was generally perceived to cause mild infections in adults. ZIKV isolate (Asian lineage) [11] to cross the BBB and infect human neural cells.
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