biostudies-literatureCheng YEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los AngelesNIAID NIH HHSNINDS NIH HHSNational Institutes of HealthNIH HHS110885https://www.ebi.ac.uk/biostudies/studies/S-EPMC9230077biostudies-literatureUnknown39(9)Physiological blood-tissue barriers play a critical role in separating the circulation from immune-privileged sites and denying access to blood-borne viruses. The mechanism of virus restriction by these barriers is poorly understood. We utilize induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (iBMECs) to study virus-blood-brain barrier (BBB) interactions. These iPSC-derived cells faithfully recapitulate a striking difference in in vivo neuroinvasion by two alphavirus isolates and are selectively permissive to neurotropic flaviviruses. A model of cocultured iBMECs and astrocytes exhibits high transendothelial electrical resistance and blocks non-neurotropic flaviviruses from getting across the barrier. We find that iBMECs constitutively express an intCell reportsIntrinsic antiviral immunity of barrier cells revealed by an iPSC-derived blood-brain barrier cellular model.PMC9230077R35 NS097370R35 NS116843R21OD024896R35NS116843R21 OD024896R35NS097370U19AI131130R01 AI158704R01AI158704R01 AI146342U19 AI131130R01AI146342Natekar JPBasu MLang JLi MMHWen ZBrinton MANkembo MBXu CKumar MSong HNguyen PTTCheng YTang HQian XYao ZSanchez EMing GLMedina AfalseIntrinsic antiviral immunity of barrier cells revealed by an iPSC-derived blood-brain barrier cellular model.Physiological blood-tissue barriers play a critical role in separating the circulation from immune-privileged sites and denying access to blood-borne viruses. The mechanism of virus restriction by these barriers is poorly understood. We utilize induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (iBMECs) to study virus-blood-brain barrier (BBB) interactions. These iPSC-derived cells faithfully recapitulate a striking difference in in vivo neuroinvasion by two alphavirus isolates and are selectively permissive to neurotropic flaviviruses. A model of cocultured iBMECs and astrocytes exhibits high transendothelial electrical resistance and blocks non-neurotropic flaviviruses from getting across the barrier. We find that iBMECs constitutively express an int2022-01-01T00:00:00Z2022 May2026-05-10T01:40:33.608Z2025-02-19T02:57:19.544ZS-EPMC92300773564937910.1016/j.celrep.2022.110885