Authors: S J Richardson P Leete A J Bone A K Foulis N G Morgan
Publish Date: 2012/10/14
Volume: 56, Issue: 1, Pages: 185-193
Abstract
Immunohistochemical staining reveals that the enteroviral capsid protein VP1 is present at higher frequency in the insulincontaining islets of patients with recentonset type 1 diabetes than in controls This is consistent with epidemiological evidence suggesting that enteroviral infection may contribute to the autoimmune response in type 1 diabetes However immunostaining of VP1 is not definitive since the antibody widely used to detect the protein Clone 5D8/1 might also crossreact with additional proteins under some conditions Therefore we sought to verify that VP1 immunopositivity correlates with additional markers of viral infectionAntigen immunoreactivity was examined in formalinfixed paraffinembedded pancreases from two different collections of type 1 diabetes and control cases a historical collection from the UK and the nPOD network of Pancreatic Organ donors with Diabetes cohort from the USAVP1 immunoreactivity was present in ∼20 of insulincontaining islets of both cohorts under stringent conditions but was absent from insulindeficient islets The presence of VP1 was restricted to beta cells but only a minority of these contained the antigen The innate viral sensor protein kinase R PKR was upregulated selectively in beta cells that were immunopositive for VP1 The antiapoptotic protein myeloid cell leukaemia sequence1 Mcl1 was abundant in beta cells that were immunonegative for VP1 but Mcl1 was depleted in cells containing VP1The presence of immunoreactive VP1 within beta cells in type 1 diabetes is associated with a cellular phenotype consistent with the activation of antiviral response pathways and enhanced sensitivity to apoptosis However definitive studies confirming whether viral infections are causal to beta cell loss in human diabetes are still awaited
Keywords: