Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental 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...

Full description

Saved in:
Bibliographic Details
Published in:Pathogens (Basel) 2021-04, Vol.10 (5), p.509
Main Authors: Liu, Yakun, Garron, Tania M, Chang, Qing, Su, Zhengchen, Zhou, Changcheng, Qiu, Yuan, Gong, Eric C, Zheng, Junying, Yin, Y Whitney, Ksiazek, Thomas, Brasel, Trevor, Jin, Yang, Boor, Paul, Comer, Jason E, Gong, Bin
Format: Article
Language:English
Subjects:
Alveoli
Apoptosis
Autopsy
Cell culture
co-culture
Coronaviruses
COVID-19
Endothelial cells
Epithelial cells
Epithelium
human
Immunofluorescence
lung
Lungs
Lymphocytes
Lymphocytes T
Macrophages
non-human primate
Nucleotides
Pandemics
Pathogenesis
Pathology
Respiratory distress syndrome
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Umbilical vein
Vero cells
Viral diseases
Western blotting
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental 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.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens10050509