PEVNET

Persistent virus infection as a cause of pathogenic inflammation in type 1 diabetes - an innovative research program of biobanks and expertise

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 Obiettivo del progetto (Objective)

'Type 1 diabetes is caused by an inflammatory process which damage insulin-producing beta-cells in the pancreas. It is one of the most common chronic diseases and its incidence is rapidly increasing. Due to its complications it causes a significant medical and economic burden to European society. A causal association between enterovirus and type 1 diabetes has become more and more likely. The aim of the present research programme is to create a new research strategy aligned to a concerted scientific research effort and creation of a network of unique resources which makes it possible to achieve a significant breakthrough in this field. The main focus is in the detection of persistent enterovirus infection leading to inflammation and tissue damage in the pancreas and its role in mediating the inflammatory response that causes type 1 diabetes. The goal is to take the critical steps towards therapeutic translation of research findings by employing a novel research design and synergistic networks of excellence based on the combination of a multidisciplinary research strategy and availability of unique biobanks existing in Europe. This research programme will also create a completely new type of biobank which facilitates a wide range of new analyses of fresh tissues. The programme includes a strong translational component which facilitates the ongoing efforts to develop vaccines against diabetogenic enteroviruses and other targeted therapies. The program also has a wider impact on the entire field of research on pathogen-disease associations, since the same innovative research strategy can be applied to other diseases as well. Altogether, this research program will take full advantage of the excellent biobank networks and a long tradition in biomedical and clinical research in Europe and creates an exceptional opportunity to take the final steps towards proving causality in the enterovirus-diabetes association.'

Introduzione (Teaser)

A rapid rise in diabetes incidence cannot be attributed to changes in the genetic susceptibility of the European population, but is more likely to reflect the influence of crucial environmental factors, including pathogens. This theory is being investigated by European scientists funded under the Pevnet study.

Descrizione progetto (Article)

Type 1 diabetes (T1D) affects more than 3 million Europeans and has prolonged impact as it presents in early childhood. It causes reduced life-expectancy by an average of 10 years and induces a range of associated diseases known as diabetic complications that are severe and debilitating.

Accumulating evidence suggests that there is a causal association between persistent enterovirus (EV) infection and development of inflammation that ultimately leads to T1D. The key objective of the EU-funded Pevnet project is to study this potential association and provide a rational basis for preventing and treating T1D through EV eradication.

The rationale behind the Pevnet study is that EV persistent infections and their lack of resolution are likely to be regulated by genes that modify the host's immune response against these viruses.

As a first step, partners have performed immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) to detect EVs in the pancreas of T1D patients. The same samples have come up positive for actively replicating the virus, indicating progression of EV persistence.

Regarding the role of the immune system in this viral persistence, Pevnet scientists are analysing T1D patients and controls for their innate immune responses to EVs. Correlation of these with polymorphisms in innate immune system genes will provide valuable information on viral persistence.

An important line of the work entails determining pancreatic islet inflammation during EV infection as well as the direct impact of EV on pancreas morphology and function. Analysis of the cellular infiltrate in the pancreas, coupled with identification of the molecular targets of anti-EV cytotoxic T cell responses, will unveil the nature of the pancreatic inflammation.

Ongoing work with virus-like EV particles aims to develop an effective vaccine that, when deployed in early childhood, could prevent EV infection and T1D. Combined with antiviral agents, this approach could offer significant social and economic benefits with respect to T1D healthcare.