Tropism of SARS-CoV-2 for human cortical astrocytes

Madeline G. Andrews, Tanzila Mukhtar, Ugomma C. Eze, Camille R. Simoneau, Jayden Ross, Neelroop Parikshak, Shaohui Wang, Li Zhou, Mark Koontz, Dmitry Velmeshev, Clara Vita Siebert, Kaila M. Gemenes, Takako Tabata, Yonatan Perez, Li Wang, Mohammed A. Mostajo-Radji, Martina De Majo, Kevin C. Donohue, David Shin, Jahan SalmaAlex A. Pollen, Tomasz J. Nowakowski, Erik Ullian, G. Renuka Kumar, Ethan A. Winkler, Elizabeth E. Crouch, Melanie Ott, Arnold R. Kriegstein

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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. Neurological symptoms, which range in severity, accompany as many as one-third 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 stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.

Original languageEnglish
Article numbere2122236119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number30
DOIs
StatePublished - 26 Jul 2022
Externally publishedYes

Keywords

  • Astrocyte reactivity
  • SARS-CoV-2 tropism
  • organoid models

ASJC Scopus subject areas

  • General

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