Cargando…

Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats

The Marburg and Ebola filoviruses cause a severe, often fatal, disease in humans and nonhuman primates but have only subclinical effects in bats, including Egyptian rousettes, which are a natural reservoir of Marburg virus. A fundamental question is why these viruses are highly pathogenic in humans...

Descripción completa

Detalles Bibliográficos
Autores principales: Jayaprakash, Anitha D., Ronk, Adam J., Prasad, Abhishek N., Covington, Michael F., Stein, Kathryn R., Schwarz, Toni M., Hekmaty, Saboor, Fenton, Karla A., Geisbert, Thomas W., Basler, Christopher F., Bukreyev, Alexander, Sachidanandam, Ravi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958679/
https://www.ncbi.nlm.nih.gov/pubmed/36851566
http://dx.doi.org/10.3390/v15020350
_version_ 1784895084497469440
author Jayaprakash, Anitha D.
Ronk, Adam J.
Prasad, Abhishek N.
Covington, Michael F.
Stein, Kathryn R.
Schwarz, Toni M.
Hekmaty, Saboor
Fenton, Karla A.
Geisbert, Thomas W.
Basler, Christopher F.
Bukreyev, Alexander
Sachidanandam, Ravi
author_facet Jayaprakash, Anitha D.
Ronk, Adam J.
Prasad, Abhishek N.
Covington, Michael F.
Stein, Kathryn R.
Schwarz, Toni M.
Hekmaty, Saboor
Fenton, Karla A.
Geisbert, Thomas W.
Basler, Christopher F.
Bukreyev, Alexander
Sachidanandam, Ravi
author_sort Jayaprakash, Anitha D.
collection PubMed
description The Marburg and Ebola filoviruses cause a severe, often fatal, disease in humans and nonhuman primates but have only subclinical effects in bats, including Egyptian rousettes, which are a natural reservoir of Marburg virus. A fundamental question is why these viruses are highly pathogenic in humans but fail to cause disease in bats. To address this question, we infected one cohort of Egyptian rousette bats with Marburg virus and another cohort with Ebola virus and harvested multiple tissues for mRNA expression analysis. While virus transcripts were found primarily in the liver, principal component analysis (PCA) revealed coordinated changes across multiple tissues. Gene signatures in kidney and liver pointed at induction of vasodilation, reduction in coagulation, and changes in the regulation of iron metabolism. Signatures of immune response detected in spleen and liver indicated a robust anti-inflammatory state signified by macrophages in the M2 state and an active T cell response. The evolutionary divergence between bats and humans of many responsive genes might provide a framework for understanding the differing outcomes upon infection by filoviruses. In this study, we outline multiple interconnected pathways that respond to infection by MARV and EBOV, providing insights into the complexity of the mechanisms that enable bats to resist the disease caused by filoviral infections. The results have the potential to aid in the development of new strategies to effectively mitigate and treat the disease caused by these viruses in humans.
format Online
Article
Text
id pubmed-9958679
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99586792023-02-26 Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats Jayaprakash, Anitha D. Ronk, Adam J. Prasad, Abhishek N. Covington, Michael F. Stein, Kathryn R. Schwarz, Toni M. Hekmaty, Saboor Fenton, Karla A. Geisbert, Thomas W. Basler, Christopher F. Bukreyev, Alexander Sachidanandam, Ravi Viruses Article The Marburg and Ebola filoviruses cause a severe, often fatal, disease in humans and nonhuman primates but have only subclinical effects in bats, including Egyptian rousettes, which are a natural reservoir of Marburg virus. A fundamental question is why these viruses are highly pathogenic in humans but fail to cause disease in bats. To address this question, we infected one cohort of Egyptian rousette bats with Marburg virus and another cohort with Ebola virus and harvested multiple tissues for mRNA expression analysis. While virus transcripts were found primarily in the liver, principal component analysis (PCA) revealed coordinated changes across multiple tissues. Gene signatures in kidney and liver pointed at induction of vasodilation, reduction in coagulation, and changes in the regulation of iron metabolism. Signatures of immune response detected in spleen and liver indicated a robust anti-inflammatory state signified by macrophages in the M2 state and an active T cell response. The evolutionary divergence between bats and humans of many responsive genes might provide a framework for understanding the differing outcomes upon infection by filoviruses. In this study, we outline multiple interconnected pathways that respond to infection by MARV and EBOV, providing insights into the complexity of the mechanisms that enable bats to resist the disease caused by filoviral infections. The results have the potential to aid in the development of new strategies to effectively mitigate and treat the disease caused by these viruses in humans. MDPI 2023-01-26 /pmc/articles/PMC9958679/ /pubmed/36851566 http://dx.doi.org/10.3390/v15020350 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jayaprakash, Anitha D.
Ronk, Adam J.
Prasad, Abhishek N.
Covington, Michael F.
Stein, Kathryn R.
Schwarz, Toni M.
Hekmaty, Saboor
Fenton, Karla A.
Geisbert, Thomas W.
Basler, Christopher F.
Bukreyev, Alexander
Sachidanandam, Ravi
Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats
title Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats
title_full Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats
title_fullStr Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats
title_full_unstemmed Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats
title_short Marburg and Ebola Virus Infections Elicit a Complex, Muted Inflammatory State in Bats
title_sort marburg and ebola virus infections elicit a complex, muted inflammatory state in bats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958679/
https://www.ncbi.nlm.nih.gov/pubmed/36851566
http://dx.doi.org/10.3390/v15020350
work_keys_str_mv AT jayaprakashanithad marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT ronkadamj marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT prasadabhishekn marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT covingtonmichaelf marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT steinkathrynr marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT schwarztonim marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT hekmatysaboor marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT fentonkarlaa marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT geisbertthomasw marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT baslerchristopherf marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT bukreyevalexander marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats
AT sachidanandamravi marburgandebolavirusinfectionselicitacomplexmutedinflammatorystateinbats