Infection of SC-beta cells with coxsackievirus B4 (CVB)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA605945 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11061016_1.fastq.gz | Fastqsanger.gz | |||
| SRR11061016_2.fastq.gz | Fastqsanger.gz | |||
| SRR11061017_1.fastq.gz | Fastqsanger.gz | |||
| SRR11061017_2.fastq.gz | Fastqsanger.gz | |||
| SRR11061018_1.fastq.gz | Fastqsanger.gz |
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Project description:SC-beta cells were infected with CVB and collected over a time course.
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Project description: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, hsa-miR-AMC1, 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 hsa-miR-AMC1 led to decreased CVB4 infection, suggesting a positive feedback loop wherein this microRNA further promotes viral infection. Interestingly, some predicted target genes of hsa-miR-AMC1 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 hsa-miR-AMC1 antagomir was associated with a trend toward increased insulin production. Taken together, our findings implicate novel hsa-miR-AMC1 as a potential early biomarker of coxsackievirus B4-induced type 1 diabetes and suggest that inhibiting hsa-miR-AMC1 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.
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Project description:Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the GAD β-cell antigen. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by anti-CVB T cells. Thus, our in-vitro and ex-vivo data suggest limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CVB-reactive CD8+ T cells provide biomarkers to follow response to infection and vaccination.
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