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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...

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Autores principales: Hum, Nicholas R., Bourguet, Feliza A., Sebastian, Aimy, Lam, Doris, Phillips, Ashlee M., Sanchez, Kristina R., Rasley, Amy, Loots, Gabriela G., Weilhammer, Dina R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
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.
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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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