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Persistent coxsackievirus B4 infection induces microRNA dysregulation in human pancreatic cells

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Abstract

Enterovirus infections are implicated in the development of type 1 diabetes (T1D). MicroRNAs as regulators of gene expression are involved in many physiological and pathological processes. Given that viral infections dysregulate cellular microRNAs, we investigated the impact of persistent coxsackievirus B4 infection on microRNA expression of human pancreatic cells. Next-generation sequencing was used to determine microRNA expression in PANC-1 cells persistently infected (for several weeks) with coxsackievirus B4 and uninfected control cells. Target prediction restricted to T1D risk genes was performed with miRWalk2.0. Functional annotation analysis was performed with DAVID6.7. Expression of selected microRNAs and T1D risk genes was measured by quantitative reverse-transcription polymerase chain reaction. Eighty-one microRNAs were dysregulated in persistently infected PANC-1 cells. Forty-nine of the known fifty-five T1D risk genes were predicted as putative targets of at least one of the dysregulated microRNAs. Most functional annotation terms that were enriched in these 49 putative target genes were related to the immune response or autoimmunity. mRNA levels of AFF3, BACH2, and IL7R differed significantly between persistently infected cells and uninfected cells. This is the first characterization of the microRNA expression profile changes induced by persistent coxsackievirus B4 infection in pancreatic cells. The predicted targeting of genes involved in the immune response and autoimmunity by the dysregulated microRNAs as well as the dysregulated expression of diabetes risk genes shows that persistent coxsackievirus B4 infection profoundly impacts the host cell. These data support the hypothesis of a possible link between persistent coxsackievirus B4 infection and the development of T1D.

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Abbreviations

CVB:

Type B coxsackieviruses

CVB4:

Coxsackievirus B4

Ct:

Cycle threshold

FCS:

Fetal calf serum

miRNA:

MicroRNA

T1D:

Type 1 diabetes

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Acknowledgements

This work was supported by Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche, Université Lille 2 (Equipe d’accueil 3610) and Centre Hospitalier Régional et Universitaire de Lille, and by EU FP7 (GA-261441-PEVNET): Persistent virus infection as a cause of pathogenic inflammation in type 1 diabetes—an innovative research program of biobanks and expertise).

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Authors and Affiliations

  1. Univ Lille Faculté de Médecine, CHU Lille, Laboratoire de Virologie EA3610, Lille, F-59000, France

    Ilka Engelmann, Enagnon K. Alidjinou, Antoine Bertin, Johann Bossu, Famara Sane & Didier Hober

  2. CHU Lille, Plate-forme de Génomique Fonctionnelle et Structurale, Lille, F-59000, France

    Céline Villenet & Martin Figeac

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  1. Ilka Engelmann
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  2. Enagnon K. Alidjinou
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  3. Antoine Bertin
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  4. Johann Bossu
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  5. Céline Villenet
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  7. Famara Sane
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  8. Didier Hober
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Correspondence to Didier Hober.

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Engelmann, I., Alidjinou, E.K., Bertin, A. et al. Persistent coxsackievirus B4 infection induces microRNA dysregulation in human pancreatic cells. Cell. Mol. Life Sci. 74, 3851–3861 (2017). https://doi.org/10.1007/s00018-017-2567-0

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