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Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells
The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interfero...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470047/ https://www.ncbi.nlm.nih.gov/pubmed/28473450 http://dx.doi.org/10.15252/embj.201695597 |
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author | Monel, Blandine Compton, Alex A Bruel, Timothée Amraoui, Sonia Burlaud‐Gaillard, Julien Roy, Nicolas Guivel‐Benhassine, Florence Porrot, Françoise Génin, Pierre Meertens, Laurent Sinigaglia, Laura Jouvenet, Nolwenn Weil, Robert Casartelli, Nicoletta Demangel, Caroline Simon‐Lorière, Etienne Moris, Arnaud Roingeard, Philippe Amara, Ali Schwartz, Olivier |
author_facet | Monel, Blandine Compton, Alex A Bruel, Timothée Amraoui, Sonia Burlaud‐Gaillard, Julien Roy, Nicolas Guivel‐Benhassine, Florence Porrot, Françoise Génin, Pierre Meertens, Laurent Sinigaglia, Laura Jouvenet, Nolwenn Weil, Robert Casartelli, Nicoletta Demangel, Caroline Simon‐Lorière, Etienne Moris, Arnaud Roingeard, Philippe Amara, Ali Schwartz, Olivier |
author_sort | Monel, Blandine |
collection | PubMed |
description | The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon‐induced transmembrane proteins (IFITM), a family of broad‐spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by “implosive” cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase‐independent, non‐apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV‐induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV‐infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV‐induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death. |
format | Online Article Text |
id | pubmed-5470047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54700472018-06-14 Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells Monel, Blandine Compton, Alex A Bruel, Timothée Amraoui, Sonia Burlaud‐Gaillard, Julien Roy, Nicolas Guivel‐Benhassine, Florence Porrot, Françoise Génin, Pierre Meertens, Laurent Sinigaglia, Laura Jouvenet, Nolwenn Weil, Robert Casartelli, Nicoletta Demangel, Caroline Simon‐Lorière, Etienne Moris, Arnaud Roingeard, Philippe Amara, Ali Schwartz, Olivier EMBO J Articles The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon‐induced transmembrane proteins (IFITM), a family of broad‐spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by “implosive” cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase‐independent, non‐apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV‐induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV‐infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV‐induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death. John Wiley and Sons Inc. 2017-05-04 2017-06-14 /pmc/articles/PMC5470047/ /pubmed/28473450 http://dx.doi.org/10.15252/embj.201695597 Text en © 2017 Institut Pasteur |
spellingShingle | Articles Monel, Blandine Compton, Alex A Bruel, Timothée Amraoui, Sonia Burlaud‐Gaillard, Julien Roy, Nicolas Guivel‐Benhassine, Florence Porrot, Françoise Génin, Pierre Meertens, Laurent Sinigaglia, Laura Jouvenet, Nolwenn Weil, Robert Casartelli, Nicoletta Demangel, Caroline Simon‐Lorière, Etienne Moris, Arnaud Roingeard, Philippe Amara, Ali Schwartz, Olivier Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
title | Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
title_full | Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
title_fullStr | Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
title_full_unstemmed | Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
title_short | Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
title_sort | zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470047/ https://www.ncbi.nlm.nih.gov/pubmed/28473450 http://dx.doi.org/10.15252/embj.201695597 |
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