Cargando…

Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes

Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological di...

Descripción completa

Detalles Bibliográficos
Autores principales: Quellec, Jordan, Pédarrieu, Aurélie, Piro-Mégy, Camille, Barthelemy, Jonathan, Simonin, Yannick, Salinas, Sara, Cêtre-Sossah, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10288929/
https://www.ncbi.nlm.nih.gov/pubmed/37306630
http://dx.doi.org/10.1080/22221751.2023.2207672
_version_ 1785062175603163136
author Quellec, Jordan
Pédarrieu, Aurélie
Piro-Mégy, Camille
Barthelemy, Jonathan
Simonin, Yannick
Salinas, Sara
Cêtre-Sossah, Catherine
author_facet Quellec, Jordan
Pédarrieu, Aurélie
Piro-Mégy, Camille
Barthelemy, Jonathan
Simonin, Yannick
Salinas, Sara
Cêtre-Sossah, Catherine
author_sort Quellec, Jordan
collection PubMed
description Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological disorders. However, human neuropathogenesis of Rift Valley fever virus (RVFV) is still poorly characterized. To study the interactions between RVFV and the central nervous system (CNS), we focused on RVFV infection of astrocytes, the major glial cells of the CNS that have several supporting roles including immune response regulation. We confirmed the permissiveness of astrocytes to RVFV infection and highlighted a strain-dependent infectivity. We showed that RVFV infection of astrocytes induced cell apoptosis and observed that the RVFV Non-Structural protein NSs, a known virulence factor, potentially delayed apoptosis by sequestrating activated-caspase 3 in the nucleus. Our study also showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level, but not at the protein level. This inhibition of immune response is potentially due to a NSs-dependent mechanism of mRNA nuclear export inhibition. Together, these results highlighted the direct impact of RVFV infection on the human CNS through the induction of apoptosis and a possible inhibition of early-onset immune responses that are crucial for the host survival.
format Online
Article
Text
id pubmed-10288929
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-102889292023-06-24 Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes Quellec, Jordan Pédarrieu, Aurélie Piro-Mégy, Camille Barthelemy, Jonathan Simonin, Yannick Salinas, Sara Cêtre-Sossah, Catherine Emerg Microbes Infect Research Article Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological disorders. However, human neuropathogenesis of Rift Valley fever virus (RVFV) is still poorly characterized. To study the interactions between RVFV and the central nervous system (CNS), we focused on RVFV infection of astrocytes, the major glial cells of the CNS that have several supporting roles including immune response regulation. We confirmed the permissiveness of astrocytes to RVFV infection and highlighted a strain-dependent infectivity. We showed that RVFV infection of astrocytes induced cell apoptosis and observed that the RVFV Non-Structural protein NSs, a known virulence factor, potentially delayed apoptosis by sequestrating activated-caspase 3 in the nucleus. Our study also showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level, but not at the protein level. This inhibition of immune response is potentially due to a NSs-dependent mechanism of mRNA nuclear export inhibition. Together, these results highlighted the direct impact of RVFV infection on the human CNS through the induction of apoptosis and a possible inhibition of early-onset immune responses that are crucial for the host survival. Taylor & Francis 2023-06-22 /pmc/articles/PMC10288929/ /pubmed/37306630 http://dx.doi.org/10.1080/22221751.2023.2207672 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Article
Quellec, Jordan
Pédarrieu, Aurélie
Piro-Mégy, Camille
Barthelemy, Jonathan
Simonin, Yannick
Salinas, Sara
Cêtre-Sossah, Catherine
Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
title Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
title_full Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
title_fullStr Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
title_full_unstemmed Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
title_short Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes
title_sort rift valley fever virus modulates apoptosis and immune response during infection of human astrocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10288929/
https://www.ncbi.nlm.nih.gov/pubmed/37306630
http://dx.doi.org/10.1080/22221751.2023.2207672
work_keys_str_mv AT quellecjordan riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes
AT pedarrieuaurelie riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes
AT piromegycamille riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes
AT barthelemyjonathan riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes
AT simoninyannick riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes
AT salinassara riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes
AT cetresossahcatherine riftvalleyfevervirusmodulatesapoptosisandimmuneresponseduringinfectionofhumanastrocytes