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Journal of Virology, May 2002, p. 5260-5265, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5260-5265.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Persistent Infection of Human Thymic Epithelial Cells by Coxsackievirus B4

Fabienne Brilot,1 Wassim Chehadeh,2 Chantal Charlet-Renard,1 Henri Martens,1 Vincent Geenen,1 and Didier Hober2*

Université de Liège, Centre d'Immunologie de Liège, Institut de Pathologie 4, CHU B-23, B-4000 Liège (Sart-Tilman), Belgium,1 Laboratoire de Virologie, Centre Hospitalier Régional et Universitaire, 59037 Lille, France2

Received 7 November 2001/ Accepted 11 February 2002

Persistent replication of coxsackievirus B4 (CVB4) E2 (diabetogenic) and CVB4 JBV (nondiabetogenic) strains in thymic epithelial cell (TEC)-enriched cultures (>=95%) was proved by detection of positive- and negative-strand viral RNA by reverse transcription-PCR in extracted RNA from cell cultures, VP1 capsid protein detection by immunofluorescence (IF) staining, and release of infectious particles up to 30 days after infection without obvious cytolysis. By double-IF staining, cytokeratin-containing cells were shown to be susceptible to CVB4. The persistence of CVB4 was associated with a significantly increased rate of TEC proliferation (up to 70%) after 20 days of culture and a significantly increased chronic production of immunoreactive interleukin-6 (IL-6), leukemia inhibitory factor, and granulocyte-macrophage colony-stimulating factor in supernatant after 3 days of culture. The CVB4 replication and the release of cytokines were not restricted to the CVB4 E2 diabetogenic strain and did not depend on the genetic background of the host; however, TEC were more responsive to CVB4 E2 than CVB4 JBV as far as the production of cytokines.


* Corresponding author. Mailing address: Laboratoire de Virologie, UPRES EA "Pathogenèse Virale du Diabète de Type 1," Centre Hospitalier Régional et Universitaire, Bât Paul Boulanger, 59037 Lille, France. Phone: 33 3 20 44 69 30. Fax: 33 3 20 44 52 81. E-mail: dhober{at}chru-lille.fr.


Journal of Virology, May 2002, p. 5260-5265, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5260-5265.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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