Exacerbated innate host response to SARS-CoV in aged non-human primates.

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) tha...

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Autores principales:	Saskia L Smits, Anna de Lang, Judith M A van den Brand, Lonneke M Leijten, Wilfred F van IJcken, Marinus J C Eijkemans, Geert van Amerongen, Thijs Kuiken, Arno C Andeweg, Albert D M E Osterhaus, Bart L Haagmans
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c6eeb3b20fc644658fd9c343e128b0aa
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spelling	oai:doaj.org-article:c6eeb3b20fc644658fd9c343e128b0aa2021-11-25T05:48:19ZExacerbated innate host response to SARS-CoV in aged non-human primates.1553-73661553-737410.1371/journal.ppat.1000756https://doaj.org/article/c6eeb3b20fc644658fd9c343e128b0aa2010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20140198/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-kappaB as central player, whereas expression of type I interferon (IFN)-beta is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.Saskia L SmitsAnna de LangJudith M A van den BrandLonneke M LeijtenWilfred F van IJckenMarinus J C EijkemansGeert van AmerongenThijs KuikenArno C AndewegAlbert D M E OsterhausBart L HaagmansPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 2, p e1000756 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Saskia L Smits Anna de Lang Judith M A van den Brand Lonneke M Leijten Wilfred F van IJcken Marinus J C Eijkemans Geert van Amerongen Thijs Kuiken Arno C Andeweg Albert D M E Osterhaus Bart L Haagmans Exacerbated innate host response to SARS-CoV in aged non-human primates.
description	The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-kappaB as central player, whereas expression of type I interferon (IFN)-beta is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.
format	article
author	Saskia L Smits Anna de Lang Judith M A van den Brand Lonneke M Leijten Wilfred F van IJcken Marinus J C Eijkemans Geert van Amerongen Thijs Kuiken Arno C Andeweg Albert D M E Osterhaus Bart L Haagmans
author_facet	Saskia L Smits Anna de Lang Judith M A van den Brand Lonneke M Leijten Wilfred F van IJcken Marinus J C Eijkemans Geert van Amerongen Thijs Kuiken Arno C Andeweg Albert D M E Osterhaus Bart L Haagmans
author_sort	Saskia L Smits
title	Exacerbated innate host response to SARS-CoV in aged non-human primates.
title_short	Exacerbated innate host response to SARS-CoV in aged non-human primates.
title_full	Exacerbated innate host response to SARS-CoV in aged non-human primates.
title_fullStr	Exacerbated innate host response to SARS-CoV in aged non-human primates.
title_full_unstemmed	Exacerbated innate host response to SARS-CoV in aged non-human primates.
title_sort	exacerbated innate host response to sars-cov in aged non-human primates.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/c6eeb3b20fc644658fd9c343e128b0aa
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Exacerbated innate host response to SARS-CoV in aged non-human primates.

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