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Signaling Pathway Reporter Screen with SARS-CoV-2 Proteins Identifies nsp5 as a Repressor of p53 Activity

Authors :
Abhishek Kumar
Tristan R. Grams
David C. Bloom
Zsolt Toth
Source :
Viruses, Vol 14, Iss 5, p 1039 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

The dysregulation of host signaling pathways plays a critical role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viral pathogenesis. While a number of viral proteins that can block type I IFN signaling have been identified, a comprehensive analysis of SARS-CoV-2 proteins in the regulation of other signaling pathways that can be critical for viral infection and its pathophysiology is still lacking. Here, we screened the effect of 21 SARS-CoV-2 proteins on 10 different host signaling pathways, namely, Wnt, p53, TGFβ, c-Myc, Hypoxia, Hippo, AP-1, Notch, Oct4/Sox2, and NF-κB, using a luciferase reporter assay. As a result, we identified several SARS-CoV-2 proteins that could act as activators or inhibitors for distinct signaling pathways in the context of overexpression in HEK293T cells. We also provided evidence for p53 being an intrinsic host restriction factor of SARS-CoV-2. We found that the overexpression of p53 is capable of reducing virus production, while the main viral protease nsp5 can repress the transcriptional activity of p53, which depends on the protease function of nsp5. Taken together, our results provide a foundation for future studies, which can explore how the dysregulation of specific signaling pathways by SARS-CoV-2 proteins can control viral infection and pathogenesis.

Details

Language :
English
ISSN :
19994915
Volume :
14
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.1461ff9e59634663a298af7856dcbe0c
Document Type :
article
Full Text :
https://doi.org/10.3390/v14051039