A Human 3D neural assembloid model for SARS-CoV-2 infection


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.

Authors Wang L, Sievert D, Clark AE, Federman H, Gastfriend BD, Shusta E, Palecek SP, Carlin AF, Gleeson J
Journal bioRxiv : the preprint server for biology
Publication Date 2021 Feb 9;
PubMed 33594369
PubMed Central PMC7885921
DOI 10.1101/2021.02.09.430349

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