title: Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes.
abstract: Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated.
  
  
  
  A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome.
  
  
  
  The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR.
  
  
  
  Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.
authors.affiliation: a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
authors.forename: E K
authors.initials: EK
authors.lastname: Alidjinou
authors.affiliation: a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
authors.forename: I
authors.initials: I
authors.lastname: Engelmann
authors.affiliation: a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
authors.forename: J
authors.initials: J
authors.lastname: Bossu
authors.affiliation: b Plate-forme de Génomique Fonctionnelle et Structurale , CHU de Lille , France.
authors.forename: C
authors.initials: C
authors.lastname: Villenet
authors.affiliation: b Plate-forme de Génomique Fonctionnelle et Structurale , CHU de Lille , France.
authors.forename: M
authors.initials: M
authors.lastname: Figeac
authors.affiliation: a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
authors.forename: M-B
authors.initials: MB
authors.lastname: Romond
authors.affiliation: a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
authors.forename: F
authors.initials: F
authors.lastname: Sané
authors.affiliation: a Univ Lille, CHU Lille, Laboratoire de Virologie EA3610 , Lille , France.
authors.forename: D
authors.initials: D
authors.lastname: Hober
mesh_terms: D045744:Cell Line, Tumor; D003384:Coxsackievirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D029822:Enterovirus B, Human / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000821:virology; D010183:Pancreatic Ducts / Q000166:cytology* / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein
keywords: CAR; Coxsackievirus B4; PDX-1; miRNA; pancreatic cells; persistence