For decades, investigators have considered type 1 diabetes (T1D) a disease whose development was influenced in large part by the environment. While many environmental influences have been posited for their putative association with the disease, none have seen more interest and supporting data than viruses (in general) and enteroviruses (in particular). The reasons underlying a failure to make firm associations with viruses are many, but historically have included technological hurdles allowing for their identification. Therefore, we are using metagenomics to identify and characterize the entire complement of viruses associated with prospective samples from subjects in the TEDDY (The Environmental Determinants of Diabetes in the Young) cohort.
The TEDDY microbiome and viral metagenomics study will examine >18,000 stool, plasma and peripheral blood mononuclear cell samples in individuals at risk for T1D. We are applying existing and novel technologies to difficult to obtain subject groups, and we are including a dual approach viral metagenomics strategy to culture, amplify and isolate virus sequences that may be present in very low copy number (i.e., rare). Our approach is focused not only on Type B enteroviruses that have long been associated with T1D but it will potentially also detect and identify all known viruses. If any enteroviruses are discovered we will determine whether they contain deletions in their genomethat have been previously described with persistent virus infection in humans and mouse models. In sum, this work will apply the most sensitive and effective methods currently available for detection of viruses in clinical samples and will help to determine more definitively if Type B enteroviruses or any other virus is associated with the development of T1D.
TEDDY is funded by DK 63829, 63861, 63821, 63865, 63863, 63836, 63790 and UC4DK095300 and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Juvenile Diabetes Research Foundation (JDRF), and Centers for Disease Control and Prevention (CDC).