Title: Coxsackievirus B5 Infection Induces Dysregulation of microRNAs Predicted to Target Known Type 1 Diabetes Risk Genes in Human Pancreatic Islets
Authors: Kim, KW
Ho, A
Alshabee-Akil, A
Hardikar, AA
Kay, TWH
Rawlinson, WD
Craig, ME
Issue Year: 2016
Publisher AMER DIABETES ASSOC
Series Diabetes:
Abstract Extensive research has identified enterovirus (EV) infections as key environmental triggers of type 1 diabetes. However, the underlying molecular mechanisms via which EVs contribute to the pathogenesis of type 1 diabetes remain unclear. Given that EVs dysregulate host microRNAs (miRNAs), which function as key regulators of beta-cell biology, we investigated the impact of coxsackievirus B5 (CVB5) infection on the cellular expression of miRNAs within human islets. Using high throughput quantitative PCR nanofluidics arrays, the expression of 754 miRNAs was examined in CVB5-infected human pancreatic islets. In total, 33 miRNAs were significantly dysregulated (>= threefold difference) in the infected compared with control islets (P < 0.05). Subsequently, these differentially expressed miRNAs were predicted to target mRNAs of 57 known type 1 diabetes risk genes that collectively mediate various biological processes, including the regulation of cell proliferation, cytokine production, the innate immune response, and apoptosis. In conclusion, we report the first global miRNA expression profiling of CVB5-infected human pancreatic islets. We propose that EVs disrupt the miRNA-directed suppression of proinflammatory factors within beta-cells, thereby resulting in an exacerbated antiviral immune response that promotes beta-cell destruction and eventual type 1 diabetes.
URI: https://publications.svi.edu.au/publications/6740
ISSN
Other Identifiers 10.2337/db15-0956
Publication type Article