In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 6 ( 2021-6-28), p. e1009687-
Abstract:
COVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine protease TMPRSS2 has been shown to be important for S protein priming and viral entry, however, little is known about its regulation. SPINT2 is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibit TMPRSS2 . Here, we explored the existence of a co-regulation between SPINT2 / TMPRSS2 and found a tightly regulated protease/inhibitor expression balance across tissues. We found that SPINT2 negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load after SPINT2 knockdown, while overexpression lead to a drastic reduction of the viral load. Additionally, we evaluated the expression of SPINT2 in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009687
DOI:
10.1371/journal.ppat.1009687.g001
DOI:
10.1371/journal.ppat.1009687.g002
DOI:
10.1371/journal.ppat.1009687.g003
DOI:
10.1371/journal.ppat.1009687.g004
DOI:
10.1371/journal.ppat.1009687.g005
DOI:
10.1371/journal.ppat.1009687.g006
DOI:
10.1371/journal.ppat.1009687.g007
DOI:
10.1371/journal.ppat.1009687.t001
DOI:
10.1371/journal.ppat.1009687.t002
DOI:
10.1371/journal.ppat.1009687.s001
DOI:
10.1371/journal.ppat.1009687.s002
DOI:
10.1371/journal.ppat.1009687.s003
DOI:
10.1371/journal.ppat.1009687.s004
DOI:
10.1371/journal.ppat.1009687.s005
DOI:
10.1371/journal.ppat.1009687.s006
DOI:
10.1371/journal.ppat.1009687.s007
DOI:
10.1371/journal.ppat.1009687.s008
DOI:
10.1371/journal.ppat.1009687.s009
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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