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

Pathogens

卷:10

Y.Whitney Yin¹  Trevor Brasel²  JasonE. Comer²  TaniaM. Garron²  Junying Zheng³  Yuan Qiu⁴  Changcheng Zhou⁴  Thomas Ksiazek⁴  Qing Chang⁴  Bin Gong⁴  Yakun Liu⁴  EricC. Gong⁴  Zhengchen Su⁴  Paul Boor⁴  Yang Jin⁵ 

[1] Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA;

[2] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA;

[3] Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA;

[4] Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA;

[5] Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Medical Campus, Boston, MA 02118, USA;

关键词: SARS-CoV-2;    apoptosis;    lung;    human;    non-human primate;    co-culture;   

DOI  :  10.3390/pathogens10050509

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown