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A Human 3D neural assembloid model for SARS-CoV-2 infection.
Wang, Lu; Sievert, David; Gleeson, Joseph; Clark, Alex E; Carlin, Aaron F; Federman, Hannah; Gastfriend, Benjamin D; Shusta, Eric; Palecek, Sean P.
Afiliación
  • Wang L; Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, 92123, USA.
  • Sievert D; Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, 92123, USA.
  • Gleeson J; Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, 92123, USA; Department for Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA.
  • Clark AE; Department of Medicine; University of California San Diego, School of Medicine, La Jolla, CA, 92093, USA.
  • Carlin AF; Department of Medicine; University of California San Diego, School of Medicine, La Jolla, CA, 92093, USA.
  • Federman H; Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University, Newark, NJ, 07103, USA.
  • Gastfriend BD; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • Shusta E; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • Palecek SP; Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Res Sq ; 2021 Feb 12.
Article en En | MEDLINE | ID: mdl-33594354
Clinical evidence suggests the central nervous system (CNS) is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although mechanisms remain unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points 1 . Here we show that pericyte-like cells (PLCs), when integrated into a cortical organoid, are capable of infection with authentic SARS-CoV-2. Prior to infection, PLCs elicited astrocytic maturation and production of basement membrane components, features attributed to pericyte functions in vivo. While traditional cortical organoids showed little evidence of infection, PLCs within cortical organoids served as viral 'replication hubs', with virus spreading to astrocytes and mediating inflammatory type I interferon transcriptional responses. Therefore, PLC-containing cortical organoids (PCCOs) represent a new 'assembloid' model 2 that supports SARS-CoV-2 entry and replication in neural tissue, and PCCOs serve as an experimental model for neural infection.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos