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CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells
The neurotropic Japanese encephalitis virus (JEV) is responsible for Japanese encephalitis, an uncontrolled inflammatory disease of the central nervous system. Microglia cells are the unique innate immune cell type populating the brain that cross-communicate with neurons via the CX(3)CR1-CX(3)CL1 ax...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423114/ https://www.ncbi.nlm.nih.gov/pubmed/30886214 http://dx.doi.org/10.1038/s41598-019-41302-1 |
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author | Lannes, Nils Garcia-Nicolàs, Obdullio Démoulins, Thomas Summerfield, Artur Filgueira, Luis |
author_facet | Lannes, Nils Garcia-Nicolàs, Obdullio Démoulins, Thomas Summerfield, Artur Filgueira, Luis |
author_sort | Lannes, Nils |
collection | PubMed |
description | The neurotropic Japanese encephalitis virus (JEV) is responsible for Japanese encephalitis, an uncontrolled inflammatory disease of the central nervous system. Microglia cells are the unique innate immune cell type populating the brain that cross-communicate with neurons via the CX(3)CR1-CX(3)CL1 axis. However, microglia may serve as a viral reservoir for JEV. Human microglia are able to transmit JEV infectivity to neighbouring cells in a cell-to-cell contact-dependent manner. Using JEV-treated human blood monocyte-derived microglia, the present study investigates molecular mechanisms behind cell-to-cell virus transmission by human microglia. For that purpose, JEV-associated microglia were co-cultured with JEV susceptible baby hamster kidney cells under various conditions. Here, we show that microglia hosting JEV for up to 10 days were able to transmit the virus to susceptible cells. Interestingly, neutralizing anti-JEV antibodies did not completely abrogate cell-to-cell virus transmission. Hence, intracellular viral RNA could be a contributing source of infectious virus material upon intercellular interactions. Importantly, the CX(3)CL1-CX(3)CR1 axis was a key regulator of cell-to-cell virus transmission from JEV-hosting human microglia. Our findings suggest that human microglia may be a source of infection for neuronal populations and sustain JEV brain pathogenesis in long-term infection. Moreover, the present work emphasizes on the critical role of the CX(3)CR1-CX(3)CL1 axis in JEV pathogenesis mediating transmission of infectious genomic JEV RNA. |
format | Online Article Text |
id | pubmed-6423114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64231142019-03-26 CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells Lannes, Nils Garcia-Nicolàs, Obdullio Démoulins, Thomas Summerfield, Artur Filgueira, Luis Sci Rep Article The neurotropic Japanese encephalitis virus (JEV) is responsible for Japanese encephalitis, an uncontrolled inflammatory disease of the central nervous system. Microglia cells are the unique innate immune cell type populating the brain that cross-communicate with neurons via the CX(3)CR1-CX(3)CL1 axis. However, microglia may serve as a viral reservoir for JEV. Human microglia are able to transmit JEV infectivity to neighbouring cells in a cell-to-cell contact-dependent manner. Using JEV-treated human blood monocyte-derived microglia, the present study investigates molecular mechanisms behind cell-to-cell virus transmission by human microglia. For that purpose, JEV-associated microglia were co-cultured with JEV susceptible baby hamster kidney cells under various conditions. Here, we show that microglia hosting JEV for up to 10 days were able to transmit the virus to susceptible cells. Interestingly, neutralizing anti-JEV antibodies did not completely abrogate cell-to-cell virus transmission. Hence, intracellular viral RNA could be a contributing source of infectious virus material upon intercellular interactions. Importantly, the CX(3)CL1-CX(3)CR1 axis was a key regulator of cell-to-cell virus transmission from JEV-hosting human microglia. Our findings suggest that human microglia may be a source of infection for neuronal populations and sustain JEV brain pathogenesis in long-term infection. Moreover, the present work emphasizes on the critical role of the CX(3)CR1-CX(3)CL1 axis in JEV pathogenesis mediating transmission of infectious genomic JEV RNA. Nature Publishing Group UK 2019-03-18 /pmc/articles/PMC6423114/ /pubmed/30886214 http://dx.doi.org/10.1038/s41598-019-41302-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lannes, Nils Garcia-Nicolàs, Obdullio Démoulins, Thomas Summerfield, Artur Filgueira, Luis CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells |
title | CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells |
title_full | CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells |
title_fullStr | CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells |
title_full_unstemmed | CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells |
title_short | CX(3)CR1-CX(3)CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells |
title_sort | cx(3)cr1-cx(3)cl1-dependent cell-to-cell japanese encephalitis virus transmission by human microglial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423114/ https://www.ncbi.nlm.nih.gov/pubmed/30886214 http://dx.doi.org/10.1038/s41598-019-41302-1 |
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