Considerable circumstantial evidence has accumulated to suggest that infection of pancreatic islet beta cells by a specific type of viruses known as enteroviruses may contribute to the development of autoimmunity in some patients with T1D. This is important since, if verified in a majority of cases, it may provide a means to minimize the future development of T1D in susceptible individuals via a targeted vaccination program. The evidence implicating enteroviral infection of pancreatic beta cells has arisen from a variety of sources including the successful isolation of live enteroviral strains from within the pancreases of individuals with T1D as well as the detection of a protein known as Vp1 that is specific to this virus. The objective of this study was to confirm the original results using better detection methodology, and to confirm the association of the Vp1 protein in the islet beta cells of patients with recent-onset T1D with an underlying viral infection. JDRF nPOD samples were used in this study because of their better isolation conditions and shorter storage duration. In this study, the Vp1 protein was clearly detected in 80% of nPOD samples tested, which also were positive for insulin-containing islets. Additional measures consistent with a viral infection were detected in the cells with Vp1. Taken together, these data support the earlier conclusion that enteroviral infection of islet cells may be a characteristic feature of patients with T1D in the western world. The results also reveal that this feature is representative of both new onset and long standing T1D.
Ramifications for Individuals with T1D:
It has been proposed by T1D researchers working on enteroviruses that detection of a viral protein may be simply the ‘tip of the iceberg’ with regard to enteroviral association with the disease – possibly, many more cells harbor a ‘latent’ or ‘quiet’ viral infection in the pancreas during the course of T1D pathogenesis. This study further substantiates the implications of enteroviral protein detection with the activation of antiviral pathways and cell death pathways. Whether viral infection plays a causal or accelerator role in T1D pathogenesis is yet to be determined – further information on this subject will be critical to the possible prevention of T1D.
This research was performed with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative T1D research project sponsored by JDRF.
Investigators and Institutions:
This work was led by Dr. Noel Morgan at the University of Exeter Medical School in the UK.
S. J. Richardson, P. Leete, A. J. Bone, A. K. Foulis & N. G. Morgan (2013) Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1. Diabetologia 56(1):185-93 (Epub 2012 Oct 14).