Project: Enteroviruses, Type 1 Diabetes, and the Human Microbiome
Baylor College of Medicine
Richard Lloyd, Ph.D.
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 (e.g., cow’s milk, childhood vaccinations, breast feeding), no single agent or practice stands alone as being “causative”. However, of all agents, 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.
The purpose of this project is to use recently developed methods; so called “next generation deep sequencing technologies”, to identify and characterize the entire complement of viruses associated with a variety of samples from from T1D patients.
This work is divided between two large projects that are international consortia. The TEDDY project will examine 17,000 stool, plasma and peripheral blood mononuclear cell samples. The nPOD-V project will examine pancreas, spleen and peripheral lymph nodes of T1D donors. We will assess T1D patients and individuals at varying levels of risk for T1D (i.e., healthy age matched control with no T1D associated autoantibodies, T1D negative but autoantibody positive individuals at increased risk for the disease). Beyond novel technologies and difficult to obtain subject groups, our proposal carries a number of methodological strengths.
Amongst these, a dual approach procedure will be taken to 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 in addition, will detect and identify all known viruses. If any enteroviruses are discovered we will determine whether they contain deletions in their genome that 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.