{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:35:54Z","timestamp":1791272154140,"version":"4.1.0"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2012,10,15]],"date-time":"2012-10-15T00:00:00Z","timestamp":1350259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            It has been hypothesized that a disturbance of central self-tolerance to islet \u03b2 cells may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired expression of \u03b2-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 group B4 coxsackievirus (CV-B4) 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 to by the prolonged detection of intracellular positive- and negative-strand viral RNA by reverse transcription-PCR (RT-PCR) and capsid protein VP1 by immunofluorescent staining and by the release of infectious particles in culture supernatants. The chronic stage of the infection was characterized by a low proportion of VP1-positive cells (1 to 2%), whereas many cells harbored enteroviral RNA, as displayed by RT-PCR without extraction applied directly to a few cells.\n            <jats:italic>Igf2<\/jats:italic>\n            mRNA and IGF-2 protein were dramatically decreased in CV-B4 E2-infected MTE cell cultures compared with mock-infected cultures, whereas housekeeping and interleukin-6 (\n            <jats:italic>Il6<\/jats:italic>\n            ) gene expression was maintained and\n            <jats:italic>Igf1<\/jats:italic>\n            mRNA was decreased, but to a lower extent. Inoculation of CV-B3, CV-B4 JVB, or echovirus 1 resulted in a low level of IGF-2 in culture supernatants as well, whereas herpes simplex virus 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 toward islet \u03b2 cells.\n          <\/jats:p>","DOI":"10.1128\/jvi.00726-12","type":"journal-article","created":{"date-parts":[[2012,8,2]],"date-time":"2012-08-02T00:21:45Z","timestamp":1343866905000},"page":"11151-11162","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Persistent Infection of Thymic Epithelial Cells with Coxsackievirus B4 Results in Decreased Expression of Type 2 Insulin-Like Growth Factor"],"prefix":"10.1128","volume":"86","author":[{"given":"Hela","family":"Ja\u00efdane","sequence":"first","affiliation":[{"name":"Universit\u00e9 Lille 2, Facult\u00e9 de M\u00e9decine, CHRU, Laboratoire de Virologie\/EA3610, Loos-lez-Lille, France"},{"name":"Universit\u00e9 de Monastir, Laboratoire des Maladies 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