TY - JOUR
KW - Angiotensin-Converting Enzyme 2
KW - Animals
KW - Blood-Brain Barrier
KW - COVID-19
KW - Chlorocebus aethiops
KW - Choroid Plexus
KW - HEK293 Cells
KW - Humans
KW - Models, Biological
KW - organoids
KW - SARS-CoV-2
KW - Vero Cells
KW - Viral Tropism
KW - Virus Internalization
KW - apolipoprotein
KW - blood-CSF-barrier
KW - cerebral organoids
KW - choroid plexus organoids
AU - Laura Pellegrini
AU - Anna Albecka
AU - Donna L. Mallery
AU - Max J. Kellner
AU - David Paul
AU - Andrew P. Carter
AU - Leo C. James
AU - Madeline A. Lancaster
AB - Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain.
BT - Cell Stem Cell
DA - 2020-12-03
DO - 10.1016/j.stem.2020.10.001
IS - 6
LA - eng
N2 - Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain.
PY - 2020
SP - 951
EP - 961.e5
T2 - Cell Stem Cell
TI - SARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids
VL - 27
SN - 1875-9777
ER -