ArticleDiabetologia2013
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.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- The virome in early life and childhood and development of islet autoimmunity and type 1 diabetes: A systematic review and meta-analysis of observational studies.Reviews in medical virology · 2021Pooled it
- ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents.Pediatric diabetes · 2018Guideline
- Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial.Nature medicine · 2023Trial
- The role and mechanism of mesenchymal stem cells in immunomodulation of type 1 diabetes mellitus and its complications: recent research progress and challenges: a review.Stem cell research & therapy · 2025Review
- Enterovirus VP1 protein and HLA class I hyperexpression in pancreatic islet cells of organ donors with type 1 diabetes.Diabetologia · 2025Article
- Joint analysis of the nPOD-Virus Group data: the association of enterovirus with type 1 diabetes is supported by multiple markers of infection in pancreas tissue.Diabetologia · 2025Article
- Immunohistochemical Profiling of Interferon-Stimulated Genes in Histopathological Specimens: A Potential Screening Approach for Viral Infections.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2025Article
- Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes.Diabetologia · 2025Article
- Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes.medRxiv : the preprint server for health sciences · 2024Article
- Article
- Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications.International journal of molecular sciences · 2023Review
- LncRNA ARGI Contributes to Virus-Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN-Stimulated Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Live enteroviruses, but not other viruses, detected in human pancreas at the onset of type 1 diabetes in the DiViD study.Diabetologia · 2022Article
- Article
- The link between circulating follicular helper T cells and autoimmunity.Nature reviews. Immunology · 2022Review
- Persistent coxsackievirus B infection and pathogenesis of type 1 diabetes mellitus.Nature reviews. Endocrinology · 2022Review
- Modeling human T1D-associated autoimmune processes.Molecular metabolism · 2022Review
- Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells.iScience · 2022Article
- Increased Expression of Viral Sensor MDA5 in Pancreatic Islets and in Hormone-Negative Endocrine Cells in Recent Onset Type 1 Diabetic Donors.Frontiers in immunology · 2022Article
- High Prevalence of Common Human Viruses in Thyroid Tissue.Frontiers in endocrinology · 2022Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisImmunohistochemical staining reveals that the enteroviral capsid protein VP1 is present at higher frequency in the insulin-containing islets of patients with recent-onset 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 cross-react with additional proteins under some conditions. Therefore, we sought to verify that VP1 immunopositivity correlates with additional markers of viral infection.
methodsAntigen immunoreactivity was examined in formalin-fixed, paraffin-embedded, 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 USA.
resultsVP1 immunoreactivity was present in ~20% of insulin-containing islets of both cohorts under stringent conditions but was absent from insulin-deficient 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 anti-apoptotic protein myeloid cell leukaemia sequence-1 (Mcl-1) was abundant in beta cells that were immunonegative for VP1 but Mcl-1 was depleted in cells containing VP1. CONCLUSIONS/
interpretationThe 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.