Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells

Teemu Smura, Olli Natri, Petri Ylipaasto, Marika Hellman, Haider Al-Hello, Lorenzo Piemonti, Merja Roivainen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1 diabetes. In addition, the capability for rapid adaptation to different cell types suggests that, on occasion, enterovirus strains with different pathogenetic properties may arise from less pathogenic ancestors.

Original languageEnglish
Pages (from-to)188-197
Number of pages10
JournalVirus Research
Volume210
DOIs
Publication statusPublished - Dec 2 2015

Fingerprint

Enterovirus
Pancreatic Ducts
Epithelial Cells
Viruses
Growth
Enterovirus Infections
Type 1 Diabetes Mellitus
Tropism
Islets of Langerhans
CD55 Antigens
Capsid Proteins
Amino Acid Substitution
Phenotype
Amino Acids

Keywords

  • Cell tropism
  • Coxsackievirus
  • Enterovirus
  • Pancreatic duct
  • Type 1 diabetes

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

Cite this

Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells. / Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja.

In: Virus Research, Vol. 210, 02.12.2015, p. 188-197.

Research output: Contribution to journalArticle

Smura, Teemu ; Natri, Olli ; Ylipaasto, Petri ; Hellman, Marika ; Al-Hello, Haider ; Piemonti, Lorenzo ; Roivainen, Merja. / Enterovirus strain and type-specific differences in growth kinetics and virus-induced cell destruction in human pancreatic duct epithelial HPDE cells. In: Virus Research. 2015 ; Vol. 210. pp. 188-197.
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