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

PLoS Pathogens

Marinus J. C. Eijkemans¹  Albert D. M. E. Osterhaus²  Thijs Kuiken²  Geert van Amerongen²  Bart L. Haagmans²  Lonneke M. Leijten²  Anna de Lang²  Arno C. Andeweg²  Saskia L. Smits²  Judith M. A. van den Brand²  Wilfred F. van IJcken³ 

[1] Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands;Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands;Erasmus Center for Biomics, Erasmus Medical Center, Rotterdam, The Netherlands

关键词: Macaque;    Young adults;    Gene expression;    SARS coronavirus;    Transcription factors;    Virus effects on host gene expression;    Interferons;    Viral replication;   

DOI  :  10.1371/journal.ppat.1000756

学科分类：生物科学（综合）

来源: Public Library of Science

【 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-κB as central player, whereas expression of type I interferon (IFN)-β 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.

【 授权许可】

CC BY