Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection

Kim, Dongbum; Maharjan, Sony; Choi, Jun-Kyu; Akauliya, Madhav; Lee, Younghee

doi:10.4062/biomolther.2020.226

Cited by 42 publications

(44 citation statements)

References 38 publications

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“…We monitored the arginylation levels of one major cytoskeleton protein, ACTB, and we observed its increase in the first 2h after infection in Calu-3 cells, with a decrease at 48h, when apoptosis-related proteins were activated 17 . The ACTB arginylation pattern was different in infected Vero cells, as was already observed for phosphorylation 89 . Such observed difference stressed the importance to use multiple cell models to assess the cellular consequences of post-translational modifications in SARS-CoV-2 infection.…”

Section: Discussionsupporting

confidence: 62%

Protein arginylation is regulated during SARS-CoV-2 infection

Macedo-da-Silva

Rosa-Fernandes

Gomes

et al. 2021

Preprint

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In 2019, the world witnessed the onset of an unprecedented pandemic. In September 2021, the infection by SARS-CoV-2 had already been responsible for the death of more than 4 million people worldwide. Recently, we and other groups discovered that SARS-CoV-2 infection induces ER-stress and activation of unfolded protein response (UPR) pathway. The degradation of misfolded/unfolded proteins is an essential element of proteostasis and occurs mainly in lysosomes or proteasomes. The N-terminal arginylation of proteins is characterized as an inducer of ubiquitination and proteasomal degradation by the N-end rule pathway. Here we present, for the first time, data on the role of arginylation during SARS-CoV-2 infection. We studied the modulation of protein arginylation in Vero CCL-81 and Calu-3 cells infected after 2h, 6h, 12h, 24h, and 48h. A reanalysis of in vivo and in vitro public omics data combined with immunoblotting was performed to measure the levels of ATE1 and arginylated proteins. This regulation is seen specifically during infections by coronaviruses. We demonstrate that during SARS-CoV-2 infection there is an increase in the expression of the ATE1 enzyme associated with regulated levels of specific arginylated proteins. On the other hand, infected macrophages showed no ATE1 regulation. An important finding revealed that modulation of the N-end rule pathway differs between different types of infected cells. We also confirmed the potential of tannic acid to reduce viral load, and furthermore, to modulate ATE1 levels during infection. In addition, the arginylation inhibitor merbromin (MER) is also capable of both reducing viral load and reducing ATE1 levels. Taken together, these data show the importance of arginylation during the progression of SARS-CoV-2 infection and open the door for future studies that may unravel the role of ATE1 and its inhibitors in pathogen infection.

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Section: Discussionsupporting

confidence: 62%

Protein arginylation is regulated during SARS-CoV-2 infection

Macedo-da-Silva

Rosa-Fernandes

Gomes

et al. 2021

Preprint

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“…We have previously reported that SARS-CoV-2 infection induces STAT3 phosphorylation in Calu-3 cells (21), and others have demonstrated that STAT3 influences MUC1 expression in lung cancer cells (22). Therefore, we investigated the effect of STAT3 inhibitors, including AG490, JAK inhibitor I, and S3I-201, on MUC1-C expression.…”

Section: Muc1-c Expression Is Dependent On Stat3 Activation In Calu-3 Cells After Sars-cov-2 Infectionmentioning

confidence: 94%

“…SARS-CoV-2 amplification and quantification was performed as described previously with minor modifications (21,31,32), and detailed information is provided in the Supplementary Material. SARS-CoV-2 amplification and cell culture procedures were performed in biosafety level 3 (BSL-3) conditions.…”

Section: Virus Amplification and Quantificationmentioning

confidence: 99%

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MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection

Maharjan

Park

Kim

et al. 2021

BMB Rep

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels; however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients. [BMB Reports 2021; 54(8): 425-430]

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“…Calu-3 cells express ACE2 on the apical membrane domain and are infected by SARS-CoV-2 via this route. The higher number of Vero E6 infected cells is also associated with the differences in viral entry pathway and the expression of pro-apoptotic proteins, which increased drastically in these cells but not in Calu-3 cells (Banerjee et al, 2020;Murgolo et al, 2021;Park et al, 2021;Saccon et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model

Varese

Ceballos

Palacios

et al. 2021

Preprint

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There are, except for remdesivir, no approved antivirals for the treatment or prevention of SARS-CoV-2 infections. Iota-carrageenan formulated into a nasal spray has already been proven safe and effective in viral respiratory infections. We explored this antiviral activity in Calu-3, a human respiratory model cell line. A formula of iota-carrageenan and sodium chloride, as a nasal spray, already approved for human use, effectively inhibited SARS-CoV-2 infection in vitro, providing a more substantial reference for further clinical studies or developments.

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Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection

Cited by 42 publications

References 38 publications

Protein arginylation is regulated during SARS-CoV-2 infection

Protein arginylation is regulated during SARS-CoV-2 infection

MUC1-C influences cell survival in lung adenocarcinoma Calu-3 cells after SARS-CoV-2 infection

Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model

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