Enterovirus Infection and Type 1 Diabetes: Closing in on a Link?

The famous French writer Victor Hugo (1802–1885) once said: “Perseverance, secret of all triumphs!” (1). Due to the divergence seen in monozygotic twin cohorts, we know that both genetic and environmental factors must contribute to the development of human type 1 diabetes (T1D) (2,3). For many decades, we have searched for environmental triggers, but it has remained difficult to define the key players. In addition to viral infections, nutritional and hygiene conditions as well as sunlight exposure and geographical locations have all been investigated but often with inconclusive results (4). Now, we might be getting closer to identifying a key culprit, which could be enteroviral infections. In this issue of Diabetes, Krogvold et al. (5) document the presence of a low-grade enteroviral infection in pancreata from recently diagnosed patients. The importance of this study resides on the uniqueness of the six specimens examined, which were collected via partial pancreatectomy from volunteers with very recently diagnosed diabetes (3–9 weeks) as part of the Diabetes Virus Detection study (DiViD) (6). Interestingly, hyperexpression of major histocompatibility complex (MHC-I) molecules and the presence of the enteroviral capsid protein 1 (VP1) were detected in the islets from all the patients. Additional confirmation was obtained by sequencing techniques in four of the six cases. These findings indicate that infections with enteroviruses could, at least in some cases, be a precipitating key factor for the onset of T1D. The natural history tells us that T1D is an inflammatory disease affecting specifically the pancreatic islets of Langerhans, where autoantibodies to various islet antigens in many cases precede clinical diagnosis and autoreactive CD8 T cells can be documented in inflamed islets (7). Viruses have been traditionally implicated in the etiopathogenesis of the disease with no definitive proof so far. Enteroviruses are one of the main candidates because …