Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure

Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the com...

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Main Authors:	Malhotra, Shikha, Yen, Judy Y., Honko, Anna N., Garamszegi, Sara, Caballero, Ignacio S., Johnson, Joshua C., Mucker, Eric M., Trefry, John C., Hensley, Lisa E., Connor, John H.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636129/

id	pubmed-3636129
recordtype	oai_dc
spelling	pubmed-36361292013-05-01 Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure Malhotra, Shikha Yen, Judy Y. Honko, Anna N. Garamszegi, Sara Caballero, Ignacio S. Johnson, Joshua C. Mucker, Eric M. Trefry, John C. Hensley, Lisa E. Connor, John H. Research Article Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response. Public Library of Science 2013-04-25 /pmc/articles/PMC3636129/ /pubmed/23638192 http://dx.doi.org/10.1371/journal.pntd.0002171 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Malhotra, Shikha Yen, Judy Y. Honko, Anna N. Garamszegi, Sara Caballero, Ignacio S. Johnson, Joshua C. Mucker, Eric M. Trefry, John C. Hensley, Lisa E. Connor, John H.
spellingShingle	Malhotra, Shikha Yen, Judy Y. Honko, Anna N. Garamszegi, Sara Caballero, Ignacio S. Johnson, Joshua C. Mucker, Eric M. Trefry, John C. Hensley, Lisa E. Connor, John H. Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure
author_facet	Malhotra, Shikha Yen, Judy Y. Honko, Anna N. Garamszegi, Sara Caballero, Ignacio S. Johnson, Joshua C. Mucker, Eric M. Trefry, John C. Hensley, Lisa E. Connor, John H.
author_sort	Malhotra, Shikha
title	Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure
title_short	Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure
title_full	Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure
title_fullStr	Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure
title_full_unstemmed	Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure
title_sort	transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure
description	Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636129/
_version_	1611972670907219968

Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure

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