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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