Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators

ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human diseases caused by infection with zoonotic viral hemorrhagic fever viruses. Elucidating mechanisms of how the natural animal reservoirs of these viruses coexist with these agents without overt disease, while permitt...

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Autores principales:	Joseph Prescott, Jonathan C. Guito, Jessica R. Spengler, Catherine E. Arnold, Amy J. Schuh, Brian R. Amman, Tara K. Sealy, Lisa W. Guerrero, Gustavo F. Palacios, Mariano Sanchez-Lockhart, Cesar G. Albariño, Jonathan S. Towner
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Ebola virus Marburg virus immune response rousette bat viral hemorrhagic fever virology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/68b626d18ac14ed19dcc88f6b9b0ecd7
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spelling	oai:doaj.org-article:68b626d18ac14ed19dcc88f6b9b0ecd72021-11-15T15:22:24ZRousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators10.1128/mSphere.00728-192379-5042https://doaj.org/article/68b626d18ac14ed19dcc88f6b9b0ecd72019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00728-19https://doaj.org/toc/2379-5042ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human diseases caused by infection with zoonotic viral hemorrhagic fever viruses. Elucidating mechanisms of how the natural animal reservoirs of these viruses coexist with these agents without overt disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg virus (MARV), a filovirus and the etiological agent of the highly lethal Marburg virus disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filovirus diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat’s immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection. IMPORTANCE Marburg viruses (MARVs) cause severe human disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in virus replication and shedding, with asymptomatic control of the virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding disease are unknown. Because DC infection and modulation are important early events in human disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.Joseph PrescottJonathan C. GuitoJessica R. SpenglerCatherine E. ArnoldAmy J. SchuhBrian R. AmmanTara K. SealyLisa W. GuerreroGustavo F. PalaciosMariano Sanchez-LockhartCesar G. AlbariñoJonathan S. TownerAmerican Society for MicrobiologyarticleEbola virusMarburg virusimmune responserousette batviral hemorrhagic fevervirologyMicrobiologyQR1-502ENmSphere, Vol 4, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ebola virus Marburg virus immune response rousette bat viral hemorrhagic fever virology Microbiology QR1-502
spellingShingle	Ebola virus Marburg virus immune response rousette bat viral hemorrhagic fever virology Microbiology QR1-502 Joseph Prescott Jonathan C. Guito Jessica R. Spengler Catherine E. Arnold Amy J. Schuh Brian R. Amman Tara K. Sealy Lisa W. Guerrero Gustavo F. Palacios Mariano Sanchez-Lockhart Cesar G. Albariño Jonathan S. Towner Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators
description	ABSTRACT Dysregulated and maladaptive immune responses are at the forefront of human diseases caused by infection with zoonotic viral hemorrhagic fever viruses. Elucidating mechanisms of how the natural animal reservoirs of these viruses coexist with these agents without overt disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg virus (MARV), a filovirus and the etiological agent of the highly lethal Marburg virus disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filovirus diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat’s immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection. IMPORTANCE Marburg viruses (MARVs) cause severe human disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in virus replication and shedding, with asymptomatic control of the virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding disease are unknown. Because DC infection and modulation are important early events in human disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.
format	article
author	Joseph Prescott Jonathan C. Guito Jessica R. Spengler Catherine E. Arnold Amy J. Schuh Brian R. Amman Tara K. Sealy Lisa W. Guerrero Gustavo F. Palacios Mariano Sanchez-Lockhart Cesar G. Albariño Jonathan S. Towner
author_facet	Joseph Prescott Jonathan C. Guito Jessica R. Spengler Catherine E. Arnold Amy J. Schuh Brian R. Amman Tara K. Sealy Lisa W. Guerrero Gustavo F. Palacios Mariano Sanchez-Lockhart Cesar G. Albariño Jonathan S. Towner
author_sort	Joseph Prescott
title	Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators
title_short	Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators
title_full	Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators
title_fullStr	Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators
title_full_unstemmed	Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators
title_sort	rousette bat dendritic cells overcome marburg virus-mediated antiviral responses by upregulation of interferon-related genes while downregulating proinflammatory disease mediators
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/68b626d18ac14ed19dcc88f6b9b0ecd7
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Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators

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