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

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

Albert D.M.E. Osterhaus, Bart L. Haagmans, Saskia L. Smits, Geert van Amerongen, Thijs Kuiken, Judith M.A. van den Brand, Marinus J. C. Eijkemans, Arno C. Andeweg, Wilfred F. van IJcken, Anna de Lang, Lonneke M Leijten

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.

2010

DOI: 10.1371/journal.ppat.1000756

PLoS Pathogens

Public Library of Science (PLoS)

Biology (General), Immunologic diseases. Allergy