RT Journal Article
SR Electronic
T1 Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.17.427024
DO 10.1101/2021.01.17.427024
A1 Madeline G. Andrews
A1 Tanzila Mukhtar
A1 Ugomma C. Eze
A1 Camille R. Simoneau
A1 Yonatan Perez
A1 Mohammed A. Mostajo-Radji
A1 Shaohui Wang
A1 Dmitry Velmeshev
A1 Jahan Salma
A1 G. Renuka Kumar
A1 Alex A. Pollen
A1 Elizabeth E. Crouch
A1 Melanie Ott
A1 Arnold R. Kriegstein
YR 2021
UL http://biorxiv.org/content/early/2021/01/18/2021.01.17.427024.abstract
AB The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in severity, accompany a significant proportion of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 and CD147. Inhibition of DPP4 reduced infection and decreased expression of the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for human astrocytes mediated by DPP4, resulting in reactive gliosis-type injury.Competing Interest StatementThe authors have declared no competing interest.