Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes. Andrews, M. G, Mukhtar, T., Eze, U. C, Simoneau, C. R, Perez, Y., Mostajo-Radji, M. A, Wang, S., Velmeshev, D., Salma, J., Kumar, G R., Pollen, A. A, Crouch, E. E, Ott, M., & Kriegstein, A. R bioRxiv, January, 2021. abstract bibtex 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.
@ARTICLE{Andrews2021-xv,
title = "Tropism of {SARS-CoV-2} for Developing Human Cortical Astrocytes",
author = "Andrews, Madeline G and Mukhtar, Tanzila and Eze, Ugomma C and
Simoneau, Camille R and Perez, Yonatan and Mostajo-Radji,
Mohammed A and Wang, Shaohui and Velmeshev, Dmitry and Salma,
Jahan and Kumar, G Renuka and Pollen, Alex A and Crouch,
Elizabeth E and Ott, Melanie and Kriegstein, Arnold R",
abstract = "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.",
journal = "bioRxiv",
month = jan,
year = 2021,
language = "en"
}
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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.","journal":"bioRxiv","month":"January","year":"2021","language":"en","bibtex":"@ARTICLE{Andrews2021-xv,\n title = \"Tropism of {SARS-CoV-2} for Developing Human Cortical Astrocytes\",\n author = \"Andrews, Madeline G and Mukhtar, Tanzila and Eze, Ugomma C and\n Simoneau, Camille R and Perez, Yonatan and Mostajo-Radji,\n Mohammed A and Wang, Shaohui and Velmeshev, Dmitry and Salma,\n Jahan and Kumar, G Renuka and Pollen, Alex A and Crouch,\n Elizabeth E and Ott, Melanie and Kriegstein, Arnold R\",\n abstract = \"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\n readily infects a variety of cell types impacting the function of\n vital organ systems, with particularly severe impact on\n respiratory function. It proves fatal for one percent of those\n infected. Neurological symptoms, which range in severity,\n accompany a significant proportion of COVID-19 cases, indicating\n a potential vulnerability of neural cell types. To assess whether\n human cortical cells can be directly infected by SARS-CoV-2, we\n utilized primary human cortical tissue and stem cell-derived\n cortical organoids. We find significant and predominant infection\n in cortical astrocytes in both primary and organoid cultures,\n with minimal infection of other cortical populations. Infected\n astrocytes had a corresponding increase in reactivity\n characteristics, growth factor signaling, and cellular stress.\n Although human cortical cells, including astrocytes, have minimal\n ACE2 expression, we find high levels of alternative coronavirus\n receptors in infected astrocytes, including DPP4 and CD147.\n Inhibition of DPP4 reduced infection and decreased expression of\n the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for\n human astrocytes mediated by DPP4, resulting in reactive\n gliosis-type injury.\",\n journal = \"bioRxiv\",\n month = jan,\n year = 2021,\n language = \"en\"\n}\n\n","author_short":["Andrews, M. G","Mukhtar, T.","Eze, U. C","Simoneau, C. R","Perez, Y.","Mostajo-Radji, M. A","Wang, S.","Velmeshev, D.","Salma, J.","Kumar, G R.","Pollen, A. A","Crouch, E. E","Ott, M.","Kriegstein, A. 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