An enterovirus strain isolated from diabetic child belongs to a genetic subcluster of echovirus 11, but is also neutralised with monotypic antisera to coxsackievirus A9

Abstract

An enterovirus strain (designated D207) isolated from a Slovakian diabetic child and originally serotyped as coxsackievirus A9 (CAV-9) was found to cause rapid cytolysis coinciding with severe functional damage of the surviving cells in primary cultures of human pancreatic islets. This finding prompted us to clone the isolate for full-length genome sequencing and molecular characterization as the prototype strain of CAV-9 is known to cause only minimal damage to insulin-producing β-cells. Based on capsid-coding sequence comparisons, the isolate turned out to be echovirus 11 (E-11). Phylogenetic analyses demonstrated that E-11/D207 was closely related to a specific subgroup B of E-11 strains known to cause uveitis. To study further antigenic properties of isolate E-11/D207 and uveitis-causing E-11 strains, neutralization experiments were carried out with CAV-9- and E-11-specific antisera. Unlike the prototype strains, the isolate E-11/D207 and uveitis-causing E-11 strains were well neutralized with both CAV-9- and E-11-specific antisera. Attempts to identify recombination of the capsid coding sequences as a reason for double-reactivity using the Simplot analysis failed to reveal major transferred motifs. However, peptide scanning technique was able to identify antigenic regions of capsid proteins of E-11/D207 as well as regions cross-reacting with an antiserum raised to CAV-9. Thus, double specificity of E-11/D207 seems to be a real characteristic shared by the phylogenetically closely related virus strains in the genetic subgroup B of E-11.

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

“…The production of CV-B5-DS strain, mouse pancreas (in vivo) adapted CV-B5-MPA strain and murine insulinoma cell adapted CV-B5-MCA strain is described elsewhere (Al-Hello et al, 2005). The strains E-9-DM (Vreugdenhil et al, 2000) and E-11-D207 (Al-Hello et al, 2008) were originally isolated from patients at the clinical onset of type 1 diabetes and passaged twice in GMK cells. The E-30 strain 14916net87 was originally isolated from an aseptic meningitis patient in the Netherlands (Savolainen et al, 2001).…”

“…Both CV-B4-JVB and the strain CV-B4-E2 (originally isolated from a patient after onset of type 1 diabetes (Yoon et al, 1979)) strains formed productive infection but did not induce cpe. Both virus growth and cytolysis were detected for CV-B5 prototype strain Faulkner and the strains DS (that is highly cytolytic in human pancreatic islets in vitro (Ylipaasto et al, 2012)), MPP (in vivo mouse pancreas adapted strain that induces chronic pancreatic inflammation, dysregulation in glucose metabolism, loss of pancreatic acinar tissue, and mild insulitis in mouse (Al-Hello et al, 2005)) and MCA (in vitro adapted to mouse insulinoma cell line, MIN6 (Al-Hello et al, 2009)), E-9 prototype Hill, laboratory strains Barty and strain DM isolated from a patient at the onset of type 1 diabetes (Vreugdenhil et al, 2000), E-11 prototype Gregory and strain D207 isolated from a stool sample of a patient at the onset of type 1 diabetes (Al-Hello et al, 2008) as well as for E-30 prototype strain Bastianni and strain 14916net87 that is highly lytic in human pancreatic islets in vitro (Roivainen et al, 2002). surface of most of the cells using immunofluorescence technique (Fig 5). The receptor for Coxsackie B viruses (Coxsackie-adenovirus receptor, CAR) was detected in the surface of a subset of cells.…”

Generation of Immature, Mature and Tolerogenic Dendritic Cells with Differing Metabolic Phenotypes

“…Tolerogenic DCs are characterized by their expression of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) containing surface receptors and ligands. Signal transduction of ITIMs containing ILT family members, ILT3 and ILT4 in tolerogenic DCs inhibit alloproliferation and drive Foxp3 + Treg expansion 10,11 . These unique properties of tolerogenic DCs lead to their profound potency in vivo, namely the ability to induce durable tolerance to transplanted allogeneic grafts and suppress the development of autoimmune diseases.…”

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

“…Despite the importance of this topic, large-scale systematic studies aimed at identifying diabetogenic enterovirus serotypes have not been performed. Previous reports of data from case reports and small patient series suggest that the CVB group viruses may include diabetogenic serotypes (1) but also that certain echovirus serotypes have been linked to type 1 diabetes (13).…”