Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

被引：277

作者：

Smits, Saskia L. ^{[1
]}

de lang, Anna ^{[1
]}

van den Brand, Judith M. A. ^{[1
]}

Leijten, Lonneke M. ^{[1
]}

van IJcken, Wilfred F. ^{[2
]}

Eijkemans, Marinus J. C. ^{[3
]}

van Amerongen, Geert ^{[1
]}

Kuiken, Thijs ^{[1
]}

Andeweg, Arno C. ^{[1
]}

Osterhaus, Albert D. M. E. ^{[1
]}

Haagmans, Bart L. ^{[1
]}

机构：

[1] Erasmus MC, Dept Virol, Rotterdam, Netherlands

[2] Erasmus MC, Erasmus Ctr Biom, Rotterdam, Netherlands

[3] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands

来源：

PLOS PATHOGENS | 2010年 / 6卷 / 02期

关键词：

ACUTE RESPIRATORY SYNDROME; INDUCED LUNG INJURY; IMMUNE-RESPONSES; OXIDATIVE STRESS; INTERFERON-GAMMA; GENE-EXPRESSION; UP-REGULATION; CORONAVIRUS; INFLAMMATION; ALPHA;

D O I：

10.1371/journal.ppat.1000756

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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-kappa B 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.

引用

页数：15

共 67 条

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