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MAVS mediates a protective immune response in the brain to Rift Valley fever virus
Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogene...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154093/ https://www.ncbi.nlm.nih.gov/pubmed/35584192 http://dx.doi.org/10.1371/journal.ppat.1010231 |
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author | Hum, Nicholas R. Bourguet, Feliza A. Sebastian, Aimy Lam, Doris Phillips, Ashlee M. Sanchez, Kristina R. Rasley, Amy Loots, Gabriela G. Weilhammer, Dina R. |
author_facet | Hum, Nicholas R. Bourguet, Feliza A. Sebastian, Aimy Lam, Doris Phillips, Ashlee M. Sanchez, Kristina R. Rasley, Amy Loots, Gabriela G. Weilhammer, Dina R. |
author_sort | Hum, Nicholas R. |
collection | PubMed |
description | Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiated robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo, Mavs(-/-) mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified defects in type I interferon and interferon responsive gene expression within microglia in Mavs(-/-) mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis. |
format | Online Article Text |
id | pubmed-9154093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-91540932022-06-01 MAVS mediates a protective immune response in the brain to Rift Valley fever virus Hum, Nicholas R. Bourguet, Feliza A. Sebastian, Aimy Lam, Doris Phillips, Ashlee M. Sanchez, Kristina R. Rasley, Amy Loots, Gabriela G. Weilhammer, Dina R. PLoS Pathog Research Article Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiated robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo, Mavs(-/-) mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified defects in type I interferon and interferon responsive gene expression within microglia in Mavs(-/-) mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis. Public Library of Science 2022-05-18 /pmc/articles/PMC9154093/ /pubmed/35584192 http://dx.doi.org/10.1371/journal.ppat.1010231 Text en © 2022 Hum et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hum, Nicholas R. Bourguet, Feliza A. Sebastian, Aimy Lam, Doris Phillips, Ashlee M. Sanchez, Kristina R. Rasley, Amy Loots, Gabriela G. Weilhammer, Dina R. MAVS mediates a protective immune response in the brain to Rift Valley fever virus |
title | MAVS mediates a protective immune response in the brain to Rift Valley fever virus |
title_full | MAVS mediates a protective immune response in the brain to Rift Valley fever virus |
title_fullStr | MAVS mediates a protective immune response in the brain to Rift Valley fever virus |
title_full_unstemmed | MAVS mediates a protective immune response in the brain to Rift Valley fever virus |
title_short | MAVS mediates a protective immune response in the brain to Rift Valley fever virus |
title_sort | mavs mediates a protective immune response in the brain to rift valley fever virus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154093/ https://www.ncbi.nlm.nih.gov/pubmed/35584192 http://dx.doi.org/10.1371/journal.ppat.1010231 |
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