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Viral triggers of Type 1 diabetes: Effects of Coxsackie B virus infection on transcriptome of trophoblast and pancreatic beta cell lines.

ABSTRACT: The epidemiological association of coxsackievirus B infection with type 1 diabetes suggests that therapeutic strategies that reduce viral load could delay or prevent disease onset. Moreover, recent studies suggest that treatment with antiviral agents against coxsackievirus B may help preserve insulin levels in type 1 diabetic patients. In the current study, we performed small RNA-sequencing to show that infection of immortalized trophoblast cells with coxsackievirus caused differential regulation of several miRNAs. One of these, N-miR376, was similarly upregulated in human pancreatic β cells infected with coxsackievirus B4. Moreover, treatment of β cells with non-cytotoxic concentrations of an antagomir that targets N-miR376 led to decreased CVB4 infection, suggesting a positive feedback loop wherein this microRNA further promotes viral infection. Interestingly, some predicted target genes of N-miR376 are shared with Hsa-miR-184, a microRNA that is known to suppress genes that regulate insulin production in pancreatic β cells. Consistently, treatment of coxsackievirus B4-infected β cells with the N-miR376 antagomir was associated with a trend toward increased insulin production. Taken together, our findings implicate novel N-miR376 as a potential early biomarker of coxsackievirus B4-induced type 1 diabetes and suggest that inhibiting N-miR376 may provide therapeutic benefit to type 1 diabetes patients. Our findings also support the use of trophoblast cells as a model for identifying microRNAs that might be useful diagnostic markers or therapeutic targets for coxsackievirus B-induced type 1 diabetes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE278756 | GEO | 2024/10/06

REPOSITORIES: GEO

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Viral triggers of Type 1 diabetes: Effects of Coxsackie B virus infection on transcriptome of trophoblast and pancreatic beta cell lines.

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