Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.226
Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection
Byoung Kwon Park1,†, Dongbum Kim1,†, Sangkyu Park2,†, Sony Maharjan1,†, Jinsoo Kim3,†, Jun-Kyu Choi2, Madhav Akauliya3, Younghee Lee2,* and Hyung-Joo Kwon1,3,*
1Institute of Medical Science, College of Medicine, Hallym University, Chuncheon 24252,
2Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644,
3Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
*E-mail: hjookwon@hallym.ac.kr (Kwon HJ), yhl4177@cbnu.ac.kr (Lee Y)
Tel: +82-33-248-2635 (Kwon HJ), +82-43-261-3387 (Lee Y)
Fax: +82-33-241-3640 (Kwon HJ), +82-43-267-2306 (Lee Y)
The first five authors contributed equally to this work.
Received: December 14, 2020; Revised: December 30, 2020; Accepted: January 4, 2021; Published online: January 28, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Signaling pathways that are essential for virus production have potential as therapeutic targets against COVID-19. In this study, we investigated cellular responses in two cell lines, Vero and Calu-3, upon SARS-CoV-2 infection and evaluated the effects of pathway-specific inhibitors on virus production. SARS-CoV-2 infection induced dephosphorylation of STAT1 and STAT3, high virus production, and apoptosis in Vero cells. However, in Calu-3 cells, SARS-CoV-2 infection induced long-lasting phosphorylation of STAT1 and STAT3, low virus production, and no prominent apoptosis. Inhibitors that target STAT3 phosphorylation and dimerization reduced SARS-CoV-2 production in Calu-3 cells, but not in Vero cells. These results suggest a necessity to evaluate cellular consequences upon SARS-CoV-2 infection using various model cell lines to find out more appropriate cells recapitulating relevant responses to SARS-CoV-2 infection in vitro.
Keywords: Apoptosis, COVID-19, SARS-CoV-2, STAT1, STAT3, STAT3 phosphorylation


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