Zika virus crosses an in vitro human blood brain barrier model

Judie B. Alimonti,
Maria Ribecco-Lutkiewicz,
Caroline Sodja,
Anna JezierskiEmail author View ORCID ID profile,
Danica B. Stanimirovic,
Qing Liu,
Arsalan S. Haqqani,
Wayne Conlan and
Mahmud Bani-Yaghoub

Fluids and Barriers of the CNS201815:15

https://doi.org/10.1186/s12987-018-0100-y

Received: 5 February 2018

Accepted: 30 April 2018

Published: 15 May 2018

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.