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.
Authors
Jordan Quellec, Aurélie Pédarrieu, Camille Piro-Mégy, Jonathan Barthelemy, Yannick Simonin, Sara Salinas, Catherine Cêtre-Sossah
- Bibliographic Reference
- Jordan Quellec, Aurélie Pédarrieu, Camille Piro-Mégy, Jonathan Barthelemy, Yannick Simonin, et al.. Rift Valley fever virus modulates apoptosis and immune response during infection of human astrocytes. Emerging microbes & infections, 2023, 12 (1), ⟨10.1080/22221751.2023.2207672⟩. ⟨hal-04157880⟩
- DOI
- https://doi.org/10.1080/22221751.2023.2207672
- Funding
- This work was supported by MESRI.
- HAL Collection
- ['CIRAD - Centre de coopération internationale en recherche agronomique pour le développement', 'Archive ouverte en agrobiosciences', 'Institut National de Recherche en Agriculture, Alimentation et Environnement', 'INRAE Occitanie Montpellier']
- HAL Identifier
- 4157891
- Institution
- ['EFS', 'Centre de Coopération Internationale en Recherche Agronomique pour le Développement', 'Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement']
- Laboratory
- Animal, Santé, Territoires, Risques et Ecosystèmes
- Published in
- France
Table of Contents
- Abstract 0
- Introduction 0
- Materials and methods 0
- Viral stocks and quantification 0
- Cell culture and viral infections 0
- Indirect immunofluorescence assays 0
- Fluorescence-activated cell sorting (FACS) assays 0
- Gene expression analysis 0
- Cytokine and chemokine quantification 0
- Nuclear mRNA export assay 0
- Interferon assay 0
- Statistical analysis 0
- Results 0
- RVFV infects and replicates in human astrocytes 0
- Infection of astrocytes by RVFV induces apoptosis but the RVFV NSs potentially delays cell death 0
- RVFV astrocyte infection increases expression of genes related to interferon type I and inflammatory responses, without upregulation at the protein level by a potential nuclear sequestration of mRNA 0
- Interferon type I response inhibits RVFV replication 0
- Discussion 0
- Acknowledgements 0
- Disclosure statement 0
- References 0
