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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010231 |
| _version_ | 1817970666650992640 |
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| author | Nicholas R Hum Feliza A Bourguet Aimy Sebastian Doris Lam Ashlee M Phillips Kristina R Sanchez Amy Rasley Gabriela G Loots Dina R Weilhammer |
| author_facet | Nicholas R Hum Feliza A Bourguet Aimy Sebastian Doris Lam Ashlee M Phillips Kristina R Sanchez Amy Rasley Gabriela G Loots Dina R Weilhammer |
| author_sort | Nicholas R Hum |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T20:38:05Z |
| format | Article |
| id | doaj.art-81cf85fca71d44c78decf6e001ebfc84 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-13T20:38:05Z |
| publishDate | 2022-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-81cf85fca71d44c78decf6e001ebfc842022-12-22T02:30:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-05-01185e101023110.1371/journal.ppat.1010231MAVS mediates a protective immune response in the brain to Rift Valley fever virus.Nicholas R HumFeliza A BourguetAimy SebastianDoris LamAshlee M PhillipsKristina R SanchezAmy RasleyGabriela G LootsDina R WeilhammerRift 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.https://doi.org/10.1371/journal.ppat.1010231 |
| spellingShingle | Nicholas R Hum Feliza A Bourguet Aimy Sebastian Doris Lam Ashlee M Phillips Kristina R Sanchez Amy Rasley Gabriela G Loots Dina R Weilhammer MAVS mediates a protective immune response in the brain to Rift Valley fever virus. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1010231 |
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