Context:
Recent studies have suggested that influenza A virus (IAV) might be involved in the aetiology of diabetes.
Objective and methods:
To address this question, we tested the ability of H1N1 pandemic IAV to infect, replicate, and damage human beta cell/pancreatic islet in vitro, and to induce pancreatic damage and/or glucose metabolism alteration in chemical and autoimmune models of beta cell damage in vivo. Moreover, we looked for direct and/or indirect evidence of correlation between IAV infection and autoimmunity/diabetes in humans.
Results:
Human H1N1 A/California/2009 derived viruses infected human pancreatic islets in vitro inducing a pro-inflammatory response associated with significant increase of CXCL9 and CXCL10 release. In vivo, infected mice showed a clear susceptibility to the virus, with its localization also in extra pulmonary organs including pancreas. Infection was able to induce mild modifications of glycaemia in C57B6 mice after chemical damage of islets, while it did not modulate the autoimmune damage of islet in NOD mice. One out of 69 nasopharyngeal swabs collected from patients at type 1 diabetes onset yielded positive results for IAV. Pancreas sections from 17 organ donors available from the Network for Pancreatic Organ donors with Diabetes showed the persistence of CXCL10 positive cell in islet autoimmunity positive subjects, but extremely rare cells stained for viral RNA and not preferentially in autoimmune subjects.
Conclusion:
Influenza H1N1 pdm strains are able to infect and replicate in mammalian pancreatic cells both in vitro and in vivo, but did not cause any functional impairment consistent with diabetes.