Arvo building, Lecture room F025, address: Lääkärinkatu 1.
Doctoral defence of M.Sc. Hanna-Riikka Honkanen
The field of science of the dissertation is Virology.
The opponent is Professor Joakim Dillner (Karolinska Institutet, Sweden). Professor Heikki Hyöty acts as the custos.
The language of the dissertation defence is English.
Epidemiology of Enteroviruses and Their Association with Type 1 Diabetes in Finland
Enteroviruses and rhinoviruses belong to the Enterovirus genus of the Picornaviridae family. The Enterovirus genus is the largest genus of Picornaviridae and includes currently 116 enterovirus and 167 rhinovirus types that affect humans. Enteroviruses are one of the most common viruses infecting humans worldwide and they cause diseases ranging from asymptomatic illnesses to severe, even fatal conditions. Enteroviruses have also been associated with the development of some chronic diseases, such as type 1 diabetes. Type 1 diabetes is an autoimmune disease, which is characterized by the immune-mediated destruction of pancreatic β cells. A preclinical phase, which is defined by the presence of diabetes-associated autoantibodies, precedes the onset of the disease. The development of type 1 diabetes is thought to be triggered by environmental factors in genetically susceptible subjects. Enteroviruses are thought to be a significant environmental factor contributing to type 1 diabetes, but the causality of this association has not been confirmed.
The purpose of this study was to evaluate the epidemiology of enteroviruses and rhinoviruses in Finland. Serological markers of infections, as well as the presence and types of enteroviruses in stool samples were analyzed. In addition, the aim was to identify enterovirus types that could be involved in the initiation of the events leading to the disease in type 1 diabetes. The identification of the enterovirus types associated with the disease process is important, since this would create opportunities to study the mechanisms of β cell damage induced by enteroviruses and it would enable the development of a preventive vaccine in the future.
The results of the current study demonstrate that a variety of enteroviruses is found in Finland. Altogether, 7.7% of stool samples collected from healthy children were positive for enterovirus in a RT-PCR screen. The most common enterovirus types belonged to species A enteroviruses. Enterovirus 71, which has caused severe outbreaks in Asia, was detected only occasionally. Rhinoviruses were found frequently in the stool samples of healthy children; 10 % of the samples were positive for rhinovirus RNA when analyzed by RT-PCR. All rhinoviruses species were represented. It was also shown that rhinoviruses could retain their infectivity in stool samples.
The association between enterovirus infections and the initiation of β-cell damage in type 1-diabetes was analyzed in two separate studies. First, neutralizing antibodies were measured against 41 different enterovirus types in serum samples of children who were positive for type 1 diabetes associated autoantibodies, and their matched controls. One enterovirus type, coxsackievirus B1, was identified as a potentially diabetes-associated virus type (OR 1.5, 95% CI 1.0–2.2, P= 0.04). In the other study, the presence of enteroviral RNA in stool samples was analyzed by RT-PCR. Compared with their healthy controls, case children had experienced more enterovirus infections before the appearance of the first type 1 diabetes associated autoantibodies. This was the first time when the presence of enteroviruses in stool samples was associated with type 1 diabetes long before the disease is diagnosed.
In conclusion, the results provide new information about the frequency and distribution of enteroviruses circulating in Finland. Several enterovirus and rhinovirus types are common in Finland, while some are rarer compared to other countries. In addition, the results confirm the association between enterovirus infections and the initiation of the β-cell damaging process. The identification of coxsackievirus B1 as an enterovirus type potentially associated with diabetes was a novel finding and offers possibilities to further explore its role in the pathogenesis of type 1 diabetes.
The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2226, Tampere University Press, Tampere 2016. ISBN 978-952-03-0264-1, ISSN 1455-1616. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1726, Tampere University Press 2016. ISBN 978-952-03-0265-8, ISSN 1456-954X.
Hanna-Riikka Honkanen, Tel. 040-753 3620, firstname.lastname@example.org