Abstract
Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 transcription. Furthermore, CV-B4 infections decreased STAT3 phosphorylation in vitro. We also showed that mice infected with CV-B4 had an altered expression of Igf2 isoforms as detected in TECs, followed by a decrease in the pro-IGF2 precursor in the thymus. Our study sheds new light on the intrathymic regulation of Igf2 transcription during CV-B4 infections and supports the hypothesis that a viral infection can disrupt central self-tolerance to insulin by decreasing Igf2 transcription in the thymic epithelium.
Highlights
insulin-like growth factor 2 (Igf2) Variant 1 (V1) mRNA was undetectable on day 1 or day 2 of culture
Owing to the lack of Igf2 V1 expression on day 2 P.I., its mRNA stability was not assessed. These results indicate that Coxsackievirus B4 (CV-B4) does not play a significant role in the post-transcriptional level of Igf2 expression and show that a decrease in Igf2 V3 mRNA is associated with a decrease in the Igf2 P3 promoter activity
MTE4-14 cell line, CV-B4 infection decreased the transcriptional activity of the murine
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The presentation of self-peptides by thymic epithelial cells (TECs) is a process by which newly developed T-cells in the thymus are selected to be tolerant to self-antigens. This process plays an essential role in the central self-tolerance to neuroendocrine functions. A defect in this process (e.g., loss of insulin expression) is the earliest event in the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D) [1]
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