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) 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.
|Persistent URL||dx.doi.org/10.1371/journal.ppat.1000756, hdl.handle.net/1765/28557|
Smits, S.L, de Lang, A, van den Brand, J.M.A, Leijten, L.M.E, van IJcken, W.F.J, Eijkemans, M.J.C, … Haagmans, B.L. (2010). Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathogens, 6(2). doi:10.1371/journal.ppat.1000756