| Title | Exacerbated innate host response to SARS-CoV in aged non-human primates |
|---|---|
| Published in | PLoS Pathogens, Vol. 6, No. 2. ISSN 1553-7366. |
| Author | Smits, S.L. (Saskia); Lang, de A. (Anna); Brand, van den J.M.A. (Judith); Leijten, L.M.E. (Lonneke); IJcken, van W.F.J. (Wilfred); Eijkemans, M.J.C. (René); Amerongen, van G. (Geert); Kuiken, T. (Thijs); Andeweg, A.C. (Arno); Osterhaus, A.D.M.E. (Ab); Haagmans, B.L. (Bart) |
| Date | 2010-02-01 |
| Language | English |
| Type | article |
| Abstract | 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-CoVinfected 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. |
| Publication | http://hdl.handle.net/1765/28557 |
| Persistent Identifier | urn:NBN:nl:ui:15-1765/28557 |
| Metadata | XML |
| Repository | Erasmus University Rotterdam |
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