Pathogenesis of influenza A(H7N9) virus in aged non-human primates. Pathogenesis of influenza A(H7N9) virus in aged non-human primates

The avian influenza A(H7N9) virus has caused high mortality in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In this study, we employed non-human primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as 20–26 years) caused more severe symptoms than infection of young animals (defined as 2 3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, one aged animal showed dysregulated proinflammatory cytokine and chemokine production, resulting in it being euthanized. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus. Overall design: Total RNA was extracted from lung samples and blood by using the RNeasy Mini Kit (Qiagen), according to the manufacturer’s protocol. RNA was labeledwith Cy3 dye with the QuickAmplabelingkit(Agilent Technologies), and hybridized to the Rhesus Macaque Gene Expression Microarray (Agilent Microarray Design Identification Number 026806; Agilent Technologies), as previously described [22]. Individual microarrays were performed for each lung sample that was collected from naïve and infected animals. Statistical analysis was performed using the LIMMA package. The log2of the intensity of each probe was background corrected and normalized between arrays (using the quantile method). Duplicate probes were averaged.