Cell-type apoptosis in lung during SARS-CoV-2 infection

Liu, Y.; Garron, T. M.; Chang, Q.; Su, Z.; Zhou, C.; Gong, E. C.; Zheng, J.; Yin, W.; Ksiazek, T.; Brasel, T.; Jin, Y.; Boor, P.; Comer, J. E.; Gong, B.

doi:10.1101/2020.12.23.424254

bioRxiv · 10.1101/2020.12.23.424254

Cell-type apoptosis in lung during SARS-CoV-2 infection

Liu, Y.·Garron, T. M.·Chang, Q.·Su, Z.·Zhou, C.·Gong, E. C.·Zheng, J.·Yin, W.·Ksiazek, T.·Brasel, T.·Jin, Y.·Boor, P.·Comer, J. E.·Gong, B.

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Abstract

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection because fatal COVID-19 cases are commonly linked to respiratory failure due to ARDS. The pathologic alteration known as diffuse alveolar damage in endothelial and epithelial cells is a critical feature of acute lung injury in ARDS. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in post-mortem lung sections from COVID-19 patients and lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence (IF) assays and western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells, but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with an EPAC1-specific activator ameliorated apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.

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Liu, Y., Garron, T. M., Chang, Q., Su, Z., Zhou, C., Gong, E. C., Zheng, J., Yin, W., Ksiazek, T., Brasel, T., Jin, Y., Boor, P., Comer, J. E., Gong, B.. 2020-12-24. Cell-type apoptosis in lung during SARS-CoV-2 infection. https://doi.org/10.1101/2020.12.23.424254

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