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SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents
Controversial reports have suggested that SARS-CoV E and 3a proteins are plasma membrane viroporins. Here, we aimed at better characterizing the cellular responses induced by these proteins. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly acqu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252541/ https://www.ncbi.nlm.nih.gov/pubmed/37296595 http://dx.doi.org/10.3390/cells12111474 |
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author | Oliveira-Mendes, Barbara B. R. Alameh, Malak Ollivier, Béatrice Montnach, Jérôme Bidère, Nicolas Souazé, Frédérique Escriou, Nicolas Charpentier, Flavien Baró, Isabelle De Waard, Michel Loussouarn, Gildas |
author_facet | Oliveira-Mendes, Barbara B. R. Alameh, Malak Ollivier, Béatrice Montnach, Jérôme Bidère, Nicolas Souazé, Frédérique Escriou, Nicolas Charpentier, Flavien Baró, Isabelle De Waard, Michel Loussouarn, Gildas |
author_sort | Oliveira-Mendes, Barbara B. R. |
collection | PubMed |
description | Controversial reports have suggested that SARS-CoV E and 3a proteins are plasma membrane viroporins. Here, we aimed at better characterizing the cellular responses induced by these proteins. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly acquired round shapes that detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this by using flow cytometry. In adhering cells expressing E or 3a protein, the whole-cell currents were not different from those of the control, suggesting that E and 3a proteins are not plasma membrane viroporins. In contrast, recording the currents on detached cells uncovered outwardly rectifying currents much larger than those observed in the control. We illustrate for the first time that carbenoxolone and probenecid block these outwardly rectifying currents; thus, these currents are most probably conducted by pannexin channels that are activated by cell morphology changes and also potentially by cell death. The truncation of C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent these outwardly rectifying currents. This suggests distinct pathways for the induction of these cellular events by the two proteins. We conclude that SARS-CoV-2 E and 3a proteins are not viroporins expressed at the plasma membrane. |
format | Online Article Text |
id | pubmed-10252541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102525412023-06-10 SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents Oliveira-Mendes, Barbara B. R. Alameh, Malak Ollivier, Béatrice Montnach, Jérôme Bidère, Nicolas Souazé, Frédérique Escriou, Nicolas Charpentier, Flavien Baró, Isabelle De Waard, Michel Loussouarn, Gildas Cells Article Controversial reports have suggested that SARS-CoV E and 3a proteins are plasma membrane viroporins. Here, we aimed at better characterizing the cellular responses induced by these proteins. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly acquired round shapes that detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this by using flow cytometry. In adhering cells expressing E or 3a protein, the whole-cell currents were not different from those of the control, suggesting that E and 3a proteins are not plasma membrane viroporins. In contrast, recording the currents on detached cells uncovered outwardly rectifying currents much larger than those observed in the control. We illustrate for the first time that carbenoxolone and probenecid block these outwardly rectifying currents; thus, these currents are most probably conducted by pannexin channels that are activated by cell morphology changes and also potentially by cell death. The truncation of C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent these outwardly rectifying currents. This suggests distinct pathways for the induction of these cellular events by the two proteins. We conclude that SARS-CoV-2 E and 3a proteins are not viroporins expressed at the plasma membrane. MDPI 2023-05-25 /pmc/articles/PMC10252541/ /pubmed/37296595 http://dx.doi.org/10.3390/cells12111474 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Oliveira-Mendes, Barbara B. R. Alameh, Malak Ollivier, Béatrice Montnach, Jérôme Bidère, Nicolas Souazé, Frédérique Escriou, Nicolas Charpentier, Flavien Baró, Isabelle De Waard, Michel Loussouarn, Gildas SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents |
title | SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents |
title_full | SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents |
title_fullStr | SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents |
title_full_unstemmed | SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents |
title_short | SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents |
title_sort | sars-cov-2 e and 3a proteins are inducers of pannexin currents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252541/ https://www.ncbi.nlm.nih.gov/pubmed/37296595 http://dx.doi.org/10.3390/cells12111474 |
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