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. © 2010 smits et al.