Abstract
It is increasingly realized that large animal models like the pig are exceptionally human like and serve as an excellent model for disease and inflammation. Pigs are fully susceptible to human influenza, share many similarities with humans regarding lung physiology and innate immune cell infiltration of the respiratory system. This study aimed at providing a better understanding of the involvement of innate immune factors and non-coding RNA in blood leukocytes during influenza A virus infection. By using the pig as a model we were able to perform highly controlled experimental infections and study early clinical signs of disease, viral titer, and transcriptional response of coding and non-coding RNA. This was completed during the first two weeks after experimental viral infection, generating information that would be difficult to obtain from human patients. Expression of a wide range of immune factors including several genes known to be centrally involved in the viral defence was quantified by high throughput qPCR (BioMark, Fluidigm). Likewise, miRNAs were quantified using the BioMark (Fluidigm) as well as by MiRCURY LNATM (Exiqon). During the first 24 hours of infection we found the expression of several antiviral genes, including interferon and interferon-related genes, to mimic key findings from human studies. Finally, several circulating miRNAs isolated from blood leukocytes was found to hold great potential as biomarkers for progression of viral lung infection. These results further consolidate the pig as a valuable model for influenza A virus infection.