Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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
_version_ 1783243698031558656
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
work_keys_str_mv AT monelblandine zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT comptonalexa zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT brueltimothee zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT amraouisonia zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT burlaudgaillardjulien zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT roynicolas zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT guivelbenhassineflorence zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT porrotfrancoise zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT geninpierre zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT meertenslaurent zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT sinigaglialaura zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT jouvenetnolwenn zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT weilrobert zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT casartellinicoletta zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT demangelcaroline zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT simonloriereetienne zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT morisarnaud zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT roingeardphilippe zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT amaraali zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells
AT schwartzolivier zikavirusinducesmassivecytoplasmicvacuolizationandparaptosislikedeathininfectedcells