Pyroptosis of syncytia formed by fusion of SARS-CoV-2 Spike and ACE2 expressing cells

Ma, H.; Zhu, Z.; Lin, H.; Wang, S.; Zhang, P.; Li, Y.; Li, L.; Wang, J.; Zhao, Y.; Han, J.

doi:10.1101/2021.02.25.432853

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bioRxiv · 10.1101/2021.02.25.432853

Pyroptosis of syncytia formed by fusion of SARS-CoV-2 Spike and ACE2 expressing cells

Ma, H.·Zhu, Z.·Lin, H.·Wang, S.·Zhang, P.·Li, Y.·Li, L.·Wang, J.·Zhao, Y.·Han, J.

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Abstract

SARS-Cov-2 infected cells fused with the ACE2-positive neighboring cells forming syncytia. However, the effect of syncytia in disease development is largely unknown. We established an in vitro cell-cell fusion system and used it to mimic the fusion of SARS-CoV-2 infected cells with ACE2-expressing cells to form syncytia. We found that Caspase-9 was activated after syncytia formation, and Caspase-3/7 was activated downstream of Caspase-9, but it triggered GSDME-dependent pyroptosis rather than apoptosis. What is more, single cell RNA-sequencing data showed that both ACE2 and GSDME were expression in alveolar type 2 cells in human lung. We propose that pyroptosis is the fate of syncytia formed by SARS-CoV-2 infected host cells and ACE2-positive cells, which indicated that lytic death of syncytia may contribute to the excessive inflammatory responses in severe COVID-19 patients.

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Ma, H., Zhu, Z., Lin, H., Wang, S., Zhang, P., Li, Y., Li, L., Wang, J., Zhao, Y., Han, J.. 2021-02-25. Pyroptosis of syncytia formed by fusion of SARS-CoV-2 Spike and ACE2 expressing cells. https://doi.org/10.1101/2021.02.25.432853

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