Final Activity Report Summary - BECAD (Characterisation of Pancreatic Beta-Cell Antiviral Defence, providing a Basis for the Development of a Novel Preventative Treatment for Type 1 Diabetes) Type 1 diabetes (T1D), also known as insulin-dependent or juvenile diabetes, is a chronic metabolic disease caused by a deficiency in the production of insulin by the pancreas islet beta-cells. The annual incidence of T1D increased more than tenfold between the years 1900 and 2000. This acceleration was particularly striking in western European countries with Finland and Sweden having the highest incidences of T1D in the world, with a range of about 50 per 100 000 per year. The long-term complications of the disease include decreased life quality and increased risk of premature death for the affected individual. At present, there are no preventative treatments for T1D and the high degree of transplant rejection and scarcity of beta-cell material hampers islet replacement strategies. The accelerated incidence of the disease; however, calls for rapid development of preventative therapies. Epidemiological data and clinical findings strongly suggest that viral infections can trigger the onset of T1D. A hypothesis, which has received much attention because of some recent supportive findings, suggests that pancreatic islet beta-cells are infected and destroyed by viral infections and that this explains, at least partially, the role of viral infection in the disease process. In order to develop preventative therapies for the disease, we need to enrich our knowledge on how a viral infection destroys insulin-producing islet beta-cells. More importantly, we must identify the mechanism, or mechanisms, by which a beta-cell can be protected from viral attack. In this research programme, we began to define the necessary mechanisms for beta-cells survival against viral attack. Antiviral defence mechanisms, normally expressed by insulin-producing islet cells, were examined in detail and the role of these defences in beta-cell survival following infection with viruses suspected to trigger T1D was carefully determined. Moreover, we determined how beta-cell antiviral defence could be modulated by factors produced by the infected host during viral infection. Our findings provided an increased understanding on how insulin-producing cells were normally protected from viral attack. We also provided a knowledge platform that could be used in order to study why some individuals failed to clear a virus infection without developing T1D.