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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/11/1474 |
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| author | Barbara B. R. Oliveira-Mendes Malak Alameh Béatrice Ollivier Jérôme Montnach Nicolas Bidère Frédérique Souazé Nicolas Escriou Flavien Charpentier Isabelle Baró Michel De Waard Gildas Loussouarn |
| author_facet | Barbara B. R. Oliveira-Mendes Malak Alameh Béatrice Ollivier Jérôme Montnach Nicolas Bidère Frédérique Souazé Nicolas Escriou Flavien Charpentier Isabelle Baró Michel De Waard Gildas Loussouarn |
| author_sort | Barbara B. R. Oliveira-Mendes |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T03:09:32Z |
| format | Article |
| id | doaj.art-633e57adb491400ea4f4c0e3ef2f4bb4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:09:32Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-633e57adb491400ea4f4c0e3ef2f4bb42023-11-18T07:40:35ZengMDPI AGCells2073-44092023-05-011211147410.3390/cells12111474SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin CurrentsBarbara B. R. Oliveira-Mendes0Malak Alameh1Béatrice Ollivier2Jérôme Montnach3Nicolas Bidère4Frédérique Souazé5Nicolas Escriou6Flavien Charpentier7Isabelle Baró8Michel De Waard9Gildas Loussouarn10L’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceTeam SOAP, CRCI2NA, INSERM, CNRS, Nantes Université, Université d’Angers, F-44000 Nantes, FranceCRCI2NA INSERM, CNRS, Nantes Université, F-44000 Nantes, FranceInstitut Pasteur, Université Paris Cité, Département de Santé Globale, F-75015 Paris, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceL’institut du Thorax, Nantes Université, CNRS, INSERM, F-44000 Nantes, FranceControversial 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.https://www.mdpi.com/2073-4409/12/11/1474COVID-19SARS-CoV-2viroporinsE protein3a proteinpannexin currents |
| spellingShingle | Barbara B. R. Oliveira-Mendes Malak Alameh Béatrice Ollivier Jérôme Montnach Nicolas Bidère Frédérique Souazé Nicolas Escriou Flavien Charpentier Isabelle Baró Michel De Waard Gildas Loussouarn SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents Cells COVID-19 SARS-CoV-2 viroporins E protein 3a protein 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 | COVID-19 SARS-CoV-2 viroporins E protein 3a protein pannexin currents |
| url | https://www.mdpi.com/2073-4409/12/11/1474 |
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