Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes

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.

Errataetall:

UpdateIn: Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2122236119. - PMID 35858406

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - year:2021

Enthalten in:

bioRxiv : the preprint server for biology - (2021) vom: 18. Jan.

Sprache:

Englisch

Beteiligte Personen:

Andrews, Madeline G [VerfasserIn]
Mukhtar, Tanzila [VerfasserIn]
Eze, Ugomma C [VerfasserIn]
Simoneau, Camille R [VerfasserIn]
Perez, Yonatan [VerfasserIn]
Mostajo-Radji, Mohammed A [VerfasserIn]
Wang, Shaohui [VerfasserIn]
Velmeshev, Dmitry [VerfasserIn]
Salma, Jahan [VerfasserIn]
Kumar, G Renuka [VerfasserIn]
Pollen, Alex A [VerfasserIn]
Crouch, Elizabeth E [VerfasserIn]
Ott, Melanie [VerfasserIn]
Kriegstein, Arnold R [VerfasserIn]

Links:

Volltext

Themen:

Preprint

Anmerkungen:

Date Revised 03.04.2024

published: Electronic

UpdateIn: Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2122236119. - PMID 35858406

Citation Status PubMed-not-MEDLINE

doi:

10.1101/2021.01.17.427024

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM320319849