Journal article
A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts
J Chen, JA Neil, JP Tan, R Rudraraju, M Mohenska, YBY Sun, E Walters, NG Bediaga, G Sun, Y Zhou, Y Li, D Drew, P Pymm, WH Tham, FJ Rossello, G Nie, X Liu, K Subbarao, JM Polo
Nature Cell Biology | Published : 2023
Open access
Abstract
SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated tr..
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Grants
Awarded by Australian Research Council
Funding Acknowledgements
We thank the staff at the ACRF Centre for Cancer Genomic Medicine at the MHTP Medical Genomics Facility for assistance with next-generation library preparation and Illumina sequencing. The schematics (Figs. 1a, 2a, 3b, 4a and Extended Data Fig 3i) were created using BioRender. J.M.P. and K.S. were supported by an MRFF grant (MRF9200007) and a DHHS Victorian Government Grant; J.M.P. by an ARC Future Fellowship and a NHMRC Ideas Grant (APP2004774); and K.S. by an NHMRC Investigator grant (APP1177174). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. W.H.T. is a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar (208693/Z/17/Z). Anti-ACE2 antibody generation was supported by the Victorian Government and the Medical Research Future Fund (MRFF) GNT2002073. The South Australian immunoGENomics Cancer Institute (SAiGENCI) received grant funding from the Australian Government.