The rapid worldwide incidence increase suggests a major role for environmental factors in the aetiology of type 1 diabetes (T1D). According to cross-sectional and prospective studies on T1D patients and/or prediabetic individuals, virus infections may be one of these. Influenza viruses are known to cause severe pancreatic damage in birds and in some mammals, and we have preliminary strong evidence that these virus growth in primary pancreatic islet (human and mouse) cultures “in vitro”. The objective of our project is to demonstrate that influenza viruses may play a role in the etiopathogenesis of T1D. Due to the interdisciplinary nature of this study, two different Research Institutes will be involved: Istituto Zooprofilattico Sperimentale delle Venezie (I Capua, PI) for the influenza virus expertise and the San Raffaele Diabetes Research Institute (L Piemonti, CoPI) for the diabetes expertise.

The overall goal of this research is to demonstrate that influenza virus infection may be involved in the etiopathogenesis of diabetes.

Specifically we will aim to:

1) Test “in vitro” the ability of influenza viruses to infect, replicate, and damage beta cell, pancreatic islet and endocrine cell

2) Test “in vivo” (mouse) the ability of influenza viruses to induce beta cell damage and/or alterations of glucose metabolism

3) Look for direct and/or indirect evidences of correlation between influenza viruses infection and autoimmunity/diabetes onset in humans

For the aim 3 we are testing the presence of influenza virus in pancreas at disease onset in T1D patients. For this purpose tissue samples are asked to the Network for Pancreatic Donors with Diabetes (nPOD). In situ hybridization will be performed to visualize viral RNA localized within cells using the Quantigene ViewRNA technique based on branched DNA signal amplification technology. Moreover the presence of influenza virus will be eventually confirmed by digital PCR and immunohystiochemistry