Viruses and Type 1 Diabetes: From Enteroviruses to the Virome (original) (raw)
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Clinical & Experimental Immunology, 2012
The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans.
Enterovirus Infection and Progression From Islet Autoimmunity to Type 1 Diabetes
Diabetes, 2010
OBJECTIVE To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical...
Enteroviruses and causality of type 1 diabetes: how close are we?
Pediatric Diabetes, 2011
General concepts Organ-specific autoimmunity frequently affects the endocrine system, including pancreatic islets. Type 1 diabetes mellitus (T1D) derives from the autoimmune destruction of insulin-secreting β-cells that is triggered by environmental factors (1, 2). Genetic predisposition accounts for 36-50% of disease susceptibility as demonstrated in monozygotic twin studies (3-5). Approximately 90% of new cases lack a family history of T1D indicating a large contribution of exogenous factors to pathogenesis. A variety of associations with viral infections have been reported for human diabetes including rubella, mumps, and cytomegalovirus. However, among investigated agents, human enteroviruses (HEVs) appear to play a prominent role (1). HEVs are extremely common RNA viruses that spread mainly through the fecal-oral route. Overall, these agents cause millions of new infections per year worldwide (6). The enterovirus genus comprises over 100 antigenically different virus types (7). The single-stranded 7.5 kb RNA enteroviral genome encodes for capsid proteins and other proteins involved in viral infectivity and replication. Capsid proteins are highly variable among HEV species and types. Neutralizing antibodies raised against capsid proteins are highly type specific but may also cross-react with related types (8). So far, there are no means for preventing T1D. Sets of well-defined autoantibodies have a strong predictive value (9, 10), but the costbenefit ratio of periodical determinations appears not to justify screening programs at the population level. At the diagnosis of T1D, a small fraction
Enteroviruses and type 1 diabetes: towards a better understanding of the relationship
Reviews in Medical Virology, 2010
Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, such as coxsackievirus B4 (CV-B4), can be associated with T1D. It has been demonstrated that enterovirus infections were significantly more prevalent in at risk individuals, such as siblings of diabetic patients, when they developed anti-β-cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV-B4 from the pancreas of diabetic patients strengthened the hypothesis of a relationship between the virus and the disease. Studies performed in vitro and in vivo in animal models helped to discover mechanisms of the infection of pancreas and other tissues, potentially able to play a role in the pathogenesis of T1D. Interestingly, it cannot be excluded that enteroviruses behave as half-devil half-angel since experimental studies suggest that, in certain conditions, these agents would be able to protect individuals against the disease. All of the plausible mechanisms by which enterovirus may be related to T1D will be reviewed here. Copyright © 2010 John Wiley & Sons, Ltd.
The association between enteroviruses and type 1 diabetes
Romanian Journal of Diabetes Nutrition and Metabolic Diseases, 2012
The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. The mechanisms leading to the disease involve complex interactions between the virus, host target tissue (pancreas) and the immune system. The following article is intended as a review of several recent information of the topic based on human studies that try to establish a connection between a viral infection and Type 1 diabetes. Through understanding better this association and it's implications in the onset of T1D potential new ways of prevention and treatment may emerge.
Type 1 diabetes mellitus and enterovirus linkage: search for associated etiopathology
The Egyptian Journal of Internal Medicine, 2017
Type 1 diabetes (T1D) is believed to have complex interplay between several enteroviruses (EVs) and host immune system disturbance induced or accelerated by viral pathogenesis. In the past two decades, there has been global upsurge in the incidence of childhood T1D, especially in those less than 5 years. Because of the ubiquity and persistence of EVs in human bowel and their tropism to pancreatic cells, they tend to express certain viral proteins that have propensity for genetic manipulation and activation of autoimmunity that could be potentially linked to T1D. In view of these, we present this review of existing literature in order to analyze the epidemiology and possible association between EV infections, host immune dysfunction, and development of autoimmunity or T1D with the view to encourage the investigation of EV infections and associated virus-induced islet cells autoimmunity and immunopathy in genetically predisposed children.