title: Persistent infection of human thymic epithelial cells by coxsackievirus B4.
abstract: Persistent replication of coxsackievirus B4 (CVB4) E2 (diabetogenic) and CVB4 JBV (nondiabetogenic) strains in thymic epithelial cell (TEC)-enriched cultures (>or=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.
authors.affiliation: Université de Liège, Centre d'Immunologie de Liège, Institut de Pathologie 4, Sart-Tilman, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
authors.forename: Wassim
authors.initials: W
authors.lastname: Chehadeh
authors.forename: Chantal
authors.initials: C
authors.lastname: Charlet-Renard
authors.forename: Henri
authors.initials: H
authors.lastname: Martens
authors.forename: Vincent
authors.initials: V
authors.lastname: Geenen
authors.forename: Didier
authors.initials: D
authors.lastname: Hober
mesh_terms: D002455:Cell Division; D002478:Cells, Cultured; D002675:Child, Preschool; D003115:Colony-Stimulating Factors / Q000032:analysis; D029822:Enterovirus B, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D006131:Growth Inhibitors / Q000032:analysis; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000032:analysis; D007633:Keratins / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland
chemical_list: D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012367:RNA, Viral; D016179:Granulocyte Colony-Stimulating Factor; D007633:Keratins