Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes.

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  • Additional Information
    • Source:
      Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE
    • Publication Information:
      Publication: 2015- : Philadelphia, PA : Taylor & Francis
      Original Publication: Austin, Tex. : Landes Bioscience
    • Subject Terms:
      Coxsackievirus Infections/*virology ; Enterovirus B, Human/*physiology ; Pancreatic Ducts/*cytology ; Pancreatic Ducts/*virology; Cell Line, Tumor ; Coxsackievirus Infections/genetics ; Coxsackievirus Infections/metabolism ; Enterovirus B, Human/genetics ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Pancreas/metabolism ; Pancreas/virology ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Virus Replication
    • Abstract:
      Introduction: 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.
      Methods: 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.
      Results: 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.
      Conclusion: 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.
    • Comments:
      Comment in: Virulence. 2017 Oct 3;8(7):1062-1065. (PMID: 28362547)
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    • Contributed Indexing:
      Keywords: CAR; Coxsackievirus B4; PDX-1; miRNA; pancreatic cells; persistence
    • Accession Number:
      0 (Homeodomain Proteins)
      0 (MicroRNAs)
      0 (Trans-Activators)
      0 (pancreatic and duodenal homeobox 1 protein)
    • Publication Date:
      Date Created: 20170124 Date Completed: 20180319 Latest Revision: 20181113
    • Publication Date:
      20221213
    • Accession Number:
      PMC5711397
    • Accession Number:
      10.1080/21505594.2017.1284735
    • Accession Number:
      28112573