Research in the Radke laboratory is focused on understanding both viral and host factors that alter innate immune responses to severe respiratory viral infection leading to acute respiratory distress syndrome (ARDS) in order to begin to design novel therapeutic treats to prevent/treat virus induced ARDS. Our studies use an emergent strain of human Adenovirus 14 (Ad14p1) which is predominant strain of Ad14 circulating around the world and is responsible for multiple outbreaks in populations annually. These infections are more severe than standard Adenovirus infections in otherwise healthy individuals and can result in severe, acute lung injury and, in some cases, ARDS which has resulted in fatalities. Syrian hamsters are permissive for human adenoviruses. We have shown that infection of Syrian hamsters with Ad14p1 infection induces a patchy bronchopneumonia and increased inflammatory cytokine expression in the lungs that is not seen following infection with prototype Ad14 strain (de Wit). We have described a novel, immunorepressive activity of Ad infected dying cells (termed Ad CPE corpses) that modulate the Ad-induced, innate immune response. Ad CPE corpse repression of macrophage-mediated inflammatory responses requires expression of the Ad protein, E1B 19/20K. Ad CPE corpses resulting from infection with Ad that lack E1B 19/20K, fail to repress Ad-induced macrophage pro-inflammatory responses and, in contrast, can induce increases in such responses. Ad14p1 infected cells express only ~20% of the E1B 19/20K protein compared to Ad14. Despite being 99.9% genetically identical there are other ways Ad14p1 differs from Ad14 besides E1B 19/20K expression. We have identified cellular miRNAs that are more abundantly expressed in Ad14 CPE corpses than in Ad14p1 CPE corpses and have been shown to play a role in down regulating pro-inflammatory signal transduction pathways and cytokine expression. Adenovirus also encode RNA molecules which can be processed by Dicer into virally encoded miRNAs. In recent studies we have shown that there is differential expression of these Ad encoded miRNAs between Ad14 and Ad14p1 infected cells. There are also scattered mutations in Ad14p1 genes that result in amino acid changes in expressed viral proteins that may alter the innate immune response during infection. Our current research is focused on how these changes in host/viral miRNA expression as well as changes in viral protein expression/function contributes to the pathogenesis of Ad14p1. We are beginning studies to understand how host factors such as diabetes result in increased morbidity/mortality from respiratory viral infections from emergent strains of Adenovirus and influenza.