Cell-type apoptosis in lung during sars-cov-2 infection

Yakun Liu, Tania M. Garron, Qing Chang, Zhengchen Su, Changcheng Zhou, Yuan Qiu, Eric C. Gong, Junying Zheng, Y. Whitney Yin, Thomas Ksiazek, Trevor Brasel, Yang Jin, Paul Boor, Jason E. Comer, Bin Gong

Research output: Contribution to journalArticlepeer-review

Abstract

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the funda-mental pathology of acute respiratory distress syndrome (ARDS) following infection. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in postmortem lung sections from COVID-19 patients and in 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 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 a novel non-cyclic nucleotide small molecule EPAC1-specific activator reduced apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.

Original languageEnglish (US)
Article number509
JournalPathogens
Volume10
Issue number5
DOIs
StatePublished - May 2021
Externally publishedYes

Keywords

  • Apoptosis
  • Co-culture
  • Endothelial cell
  • Epithelial cell
  • Human
  • Lung
  • Non-human primate
  • SARS-CoV-2
  • TUNEL assay

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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