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Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus

Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did no...

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Autores principales: Garamszegi, Sara, Yen, Judy Y., Honko, Anna N., Geisbert, Joan B., Rubins, Kathleen H., Geisbert, Thomas W., Xia, Yu, Hensley, Lisa E., Connor, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117489/
https://www.ncbi.nlm.nih.gov/pubmed/25079789
http://dx.doi.org/10.1371/journal.pntd.0003061
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author Garamszegi, Sara
Yen, Judy Y.
Honko, Anna N.
Geisbert, Joan B.
Rubins, Kathleen H.
Geisbert, Thomas W.
Xia, Yu
Hensley, Lisa E.
Connor, John H.
author_facet Garamszegi, Sara
Yen, Judy Y.
Honko, Anna N.
Geisbert, Joan B.
Rubins, Kathleen H.
Geisbert, Thomas W.
Xia, Yu
Hensley, Lisa E.
Connor, John H.
author_sort Garamszegi, Sara
collection PubMed
description Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) CCAAT/enhancer-binding protein alpha, (2) tumor protein 53, and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection.
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spelling pubmed-41174892014-08-04 Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus Garamszegi, Sara Yen, Judy Y. Honko, Anna N. Geisbert, Joan B. Rubins, Kathleen H. Geisbert, Thomas W. Xia, Yu Hensley, Lisa E. Connor, John H. PLoS Negl Trop Dis Research Article Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) CCAAT/enhancer-binding protein alpha, (2) tumor protein 53, and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection. Public Library of Science 2014-07-31 /pmc/articles/PMC4117489/ /pubmed/25079789 http://dx.doi.org/10.1371/journal.pntd.0003061 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Garamszegi, Sara
Yen, Judy Y.
Honko, Anna N.
Geisbert, Joan B.
Rubins, Kathleen H.
Geisbert, Thomas W.
Xia, Yu
Hensley, Lisa E.
Connor, John H.
Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
title Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
title_full Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
title_fullStr Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
title_full_unstemmed Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
title_short Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus
title_sort transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117489/
https://www.ncbi.nlm.nih.gov/pubmed/25079789
http://dx.doi.org/10.1371/journal.pntd.0003061
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