AUTHOR=Lalani Salima , Knudsen Joseph , Kenney James , Hober Didier , DiPersio C. Michael , Gerber Allen 

TITLE=A novel microRNA promotes coxsackievirus B4 infection of pancreatic β cells

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1414894

DOI=10.3389/fimmu.2024.1414894

ISSN=1664-3224

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 noncytotoxic 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.