title: 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.
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.
authors.affiliation: Laboratoire de Virologie/ EA3610, Université Lille 2, Faculté de Médecine, CHRU, 59120, Loos-lez-Lille, France.
authors.forename: Famara
authors.initials: F
authors.lastname: Sane
authors.forename: Delphine
authors.initials: D
authors.lastname: Caloone
authors.forename: Valéry
authors.initials: V
authors.lastname: Gmyr
authors.forename: Ilka
authors.initials: I
authors.lastname: Engelmann
authors.forename: Sandrine
authors.initials: S
authors.lastname: Belaich
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Rachel
authors.initials: R
authors.lastname: Desailloud
authors.forename: Didier
authors.initials: D
authors.lastname: Hober
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D029822:Enterovirus B, Human; D015967:Gene Expression Regulation, Viral; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008856:Microscopy, Fluorescence; D010183:Pancreatic Ducts / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D012367:RNA, Viral / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D012367:RNA, Viral; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein