Article (Scientific journals)
Persistent infection of thymic epithelial cells with coxsackievirus B4 results in a decreased expression of insulin-like growth factor 2
Jaïdane, Hela; Caloone, Delphine; Lobert, Pierre-Emmanuel et al.
2012In Journal of Virology, 86, p. 11151-11162
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Keywords :
Thymus; Coxsackievirus; IGF-2
Abstract :
[en] It has been hypothesized that a disturbance of central self-tolerance to islet β-cell may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired expression of β-cell self-antigens in thymic epithelial cells has been investigated in a murine thymic epithelial (MTE) cell line. This cell line was permissive to the diabetogenic strain CV-B4 E2 and spontaneously expressed type 2 insulin-like growth factor (Igf2), the dominant self-antigen of the insulin family. In this model, a persistent replication of CV-B4 E2 was obtained as attested by the prolonged detection of intracellular positive and negative-strand viral RNA by RT-PCR, and capsid protein VP1 by IF and by the release of infectious particles in culture supernatant fluids. The chronic stage of the infection was characterized by a low proportion of VP1-positive cells (1-2%) whereas many cells harbored enteroviral RNA as displayed by RT-PCR without extraction applied directly on a few cells. Igf2 mRNA and IGF-2 protein were dramatically decreased in CV-B4 E2-infected MTE cultures compared with mock-infected cultures, whereas housekeeping and Il6 genes expression were maintained and Igf1 mRNA was decreased but at a lower extent. Inoculation of CV-B3-, CV-B4 JVB- or Echovirus 1 resulted in a low level of IGF-2 in culture supernatant fluids as well, whereas HSV-1 stimulated the production of the protein. Thus, a persistent infection of a thymic epithelial cell line with enteroviruses, like CV-B4 E2 can result in a disturbed production of IGF-2, a protein involved in central self-tolerance towards islet β-cells.
Disciplines :
Endocrinology, metabolism & nutrition
Immunology & infectious disease
Author, co-author :
Jaïdane, Hela;  Université Lille 2 - CHRU > Laboratoire de Virologie EA3610
Caloone, Delphine;  Université Lille 2 - CHRU > Laboratoire de Virologie EA3610
Lobert, Pierre-Emmanuel;  Université de Lille 2-CHRU > Laboratoire de Virologie EA3610
Sane, Famara;  Université de Lille 2-CHRU > Laboratoire de Virologie EA3610
Dardenne, Olivier;  Université de Liège - ULiège > GIGA Research > Centre d'Immunologie
Naquet, Philippe;  Centre d'Immunologie Marseille-Luminy/INSERM-CNRS
Gharbi, Jawar;  Université de Monastir - Faculté de Pharmacie > Laboratoire des Maladies Transmissibles
Geenen, Vincent ;  Université de Liège - ULiège > Centre d'immunologie
Hober, Didier;  Université de Lille 2-CHRU > Laboratoire de Virologie EA3610
Language :
English
Title :
Persistent infection of thymic epithelial cells with coxsackievirus B4 results in a decreased expression of insulin-like growth factor 2
Publication date :
2012
Journal title :
Journal of Virology
ISSN :
0022-538X
eISSN :
1098-5514
Publisher :
American Society for Microbiology (ASM), Washington, United States - District of Columbia
Volume :
86
Pages :
11151-11162
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
FP6 Integrated Project Eurothymaide
Funders :
DG RDT - Commission Européenne. Direction Générale de la Recherche et de l'Innovation [BE]
Available on ORBi :
since 27 July 2012

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