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Coxsackievirus B4 can infect human pancreas ductal cells and persist in ductal-like cell cultures which results in inhibition of Pdx1 expression and disturbed formation of islet-like cell aggregates

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Abstract

The role of enteroviruses, especially Coxsackievirus B (CVB), in type 1 diabetes is suspected, but the mechanisms of the virus-induced or aggravated pathogenesis of the disease are unknown. The hypothesis of an enterovirus-induced disturbance of pancreatic β-cells regeneration has been investigated in the human system. The infection of human pancreas ductal cells and pancreatic duct cell line, PANC-1, with CVB4E2 has been studied. Primary ductal cells and PANC-1 cells were infectable with CVB4E2 and a RT-PCR assay without extraction displayed that a larger proportion of cells harbored viral RNA than predicted by the detection of the viral capsid protein VP1 by indirect immunofluorescence. The detection of intracellular positive- and negative-strands of enterovirus genomes in cellular extracts by RT-PCR and the presence of infectious particles in supernatant fluids during the 37 weeks of monitoring demonstrated that CVB4E2 could persist in the pancreatic duct cell line. A persistent infection of these cells resulted in an impaired expression of Pdx1, a transcription factor required for the formation of endocrine pancreas, and a disturbed formation of islet-like cell aggregates of which the viability was decreased. These data support the hypothesis of an impact of enteroviruses onto pancreatic ductal cells which are involved in the renewal of pancreatic β-cells.

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Acknowledgments

This work was supported by Ministère de l’Education Nationale de la Recherche et de la Technologie, Université Lille 2 (UPRES EA3610) and CHRU Lille and by Nord-Pas-de-Calais Région (Bureau Biologie Santé). Part of the study was funded by EU FP7 (GA-261441-PEVNET).

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Authors and Affiliations

  1. Laboratoire de Virologie/ EA3610, Université Lille 2, Faculté de Médecine, CHRU, 59120, Loos-lez-Lille, France

    Famara Sane, Delphine Caloone, Ilka Engelmann & Didier Hober

  2. Laboratoire Biothérapie du diabète, INSERM U859 CHRU de Lille, 59045, Lille, France

    Valéry Gmyr, Sandrine Belaich, Julie Kerr-Conte & François Pattou

  3. Service d’Endocrinologie-Diabétologie-Nutrition, UPJV CHU, 80054, Amiens, France

    Rachel Desailloud

  4. Laboratoire de Virologie/EA3610, Institut Hippocrate, CHRU Lille, 152 rue du Dr Yersin, 59120, Loos-Lez-Lille, France

    Didier Hober

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  1. Famara Sane
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Correspondence to Didier Hober.

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Sane, F., Caloone, D., Gmyr, V. et al. Coxsackievirus B4 can infect human pancreas ductal cells and persist in ductal-like cell cultures which results in inhibition of Pdx1 expression and disturbed formation of islet-like cell aggregates. Cell. Mol. Life Sci. 70, 4169–4180 (2013). https://doi.org/10.1007/s00018-013-1383-4

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