Tropism of SARS-CoV-2 for human cortical astrocytes.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Andrews, MG; Mukhtar, T; Eze, UC; Simoneau, CR; Ross, J; Parikshak, N; Wang, S; Zhou, L; Koontz, M; Velmeshev, D; Siebert, C-V; Gemenes, KM; Tabata, T; Perez, Y; Wang, L; Mostajo-Radji, MA; de Majo, M; Donohue, KC; Shin, D; Salma, J; Pollen, AA; Nowakowski, TJ; Ullian, E; Kumar, GR; Winkler, EA; Crouch, EE; Ott, M; Kriegstein, AR

Published Date

  • July 26, 2022

Published In

Volume / Issue

  • 119 / 30

Start / End Page

  • e2122236119 -

PubMed ID

  • 35858406

Pubmed Central ID

  • PMC9335272

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.2122236119

Language

  • eng

Conference Location

  • United States