The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However, despite decades of research, the body of evidence supporting a relationship between viral infections and initiation or acceleration of islet autoimmunity remains largely circumstantial. The most robust association with viruses and T1D involves enterovirus species, of which some strains have the ability to induce or accelerate disease in animal models. Several hypotheses have been formulated to mechanistically explain how viruses may affect islet autoimmunity and β-cell decay. The recent observation that certain viral infections, when encountered at the right time and infectious dose, can prevent autoimmune diabetes illustrates that potential relationships may be more complex than previously thought. Here, we provide a concise summary of data obtained in mouse models and humans, and identify future avenues toward a better characterization of the association between viruses and T1D.
Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4
Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice
Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population
Persistent MHV (mouse hepatitis virus) infection reduces the incidence of diabetes mellitus in non-obese diabetic mice
Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice
The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood
Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice
Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response
A search for the presence of the enteroviral capsid protein VP1 in pancreases of patients with type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis
Association of beta-cell-specific expression of endogenous retrovirus with development of insulitis and diabetes in NOD mouse
Coxsackie B, mumps, rubella, and cytomegalovirus specific IgM responses in patients with juvenile-onset insulin-dependent diabetes mellitus in Britain, Austria, and Australia
Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins
A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group
Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies
Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM
Bystander activation of cytotoxic T cells: studies on the mechanism and evaluation of in vivo significance in a transgenic mouse model
A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group
Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. EURODIAB Substudy 2 Study Group
Virus-induced diabetes in a transgenic model: role of cross-reacting viruses and quantitation of effector T cells needed to cause disease
Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology
Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets
Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes
Virus-induced autoimmune diabetes: most beta-cells die through inflammatory cytokines and not perforin from autoreactive (anti-viral) cytotoxic T-lymphocytes
Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to Coxsackie or proinsulin peptides do not crossreact with homologous counterpart
Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children
No evidence for an association of coxsackie virus infections during pregnancy and early childhood with development of islet autoantibodies in offspring of mothers or fathers with type 1 diabetes
Does the gut microbiota have a role in type 1 diabetes? Early evidence from humans and animal models of the disease
NKG2D blockade facilitates diabetes prevention by antigen-specific Tregs in a virus-induced model of diabetes
The role of the innate immune system in destruction of pancreatic beta cells in NOD mice and humans with type I diabetes
Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes
The co-occurrence of multiple sclerosis and type 1 diabetes: shared aetiologic features and clinical implication for MS aetiology
Virus antibody survey in different European populations indicates risk association between coxsackievirus B1 and type 1 diabetes
Gut microbiota translocation to the pancreatic lymph nodes triggers NOD2 activation and contributes to T1D onset
The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus
Early childhood infections precede development of beta-cell autoimmunity and type 1 diabetes in children with HLA-conferred disease risk
Manipulating Glucose Metabolism during Different Stages of Viral Pathogenesis Can Have either Detrimental or Beneficial Effects
Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells
Reduction in White Blood Cell, Neutrophil, and Red Blood Cell Counts Related to Sex, HLA, and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk for Type 1 Diabetes.
Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes
Detection and localization of viral infection in the pancreas of patients with type 1 diabetes using short fluorescently-labelled oligonucleotide probes
A Novel Approach of Identifying Immunodominant Self and Viral Antigen Cross-Reactive T Cells and Defining the Epitopes They Recognize
Enterovirus Neutralizing Antibodies, Monocyte Toll Like Receptors Expression and Interleukin Profiles Are Similar Between Non-affected and Affected Siblings From Long-Term Discordant Type 1 Diabetes Multiplex-Sib Families: The Importance of HLA Background.
Type B coxsackieviruses and central nervous system disorders: critical review of reported associations.
Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.
Autoimmune Diabetes & Tolerance
Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.