2021
DOI: 10.3390/microorganisms9020402
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Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection

Abstract: Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 tra… Show more

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Cited by 3 publications
(5 citation statements)
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“…CVB4 can infect mice following intraperitoneal or oral inoculation of the virus, as it has been previously reported by our team and others [67,68,75]. In TECs obtained from outbred mice infected intraperitoneally with CVB4, the dominant IGF2 transcript V3 and thymic IGF2 protein level had decreased [89]. Thus, CVB4 infection can modulate the expression of IGF2 in a model of TECs in vitro and can downregulate the IGF2 V3 expression and protein synthesis in vivo.…”
Section: Coxsackievirus B4 the Thymus Gland And Type 1 Diabetessupporting
confidence: 71%
See 1 more Smart Citation
“…CVB4 can infect mice following intraperitoneal or oral inoculation of the virus, as it has been previously reported by our team and others [67,68,75]. In TECs obtained from outbred mice infected intraperitoneally with CVB4, the dominant IGF2 transcript V3 and thymic IGF2 protein level had decreased [89]. Thus, CVB4 infection can modulate the expression of IGF2 in a model of TECs in vitro and can downregulate the IGF2 V3 expression and protein synthesis in vivo.…”
Section: Coxsackievirus B4 the Thymus Gland And Type 1 Diabetessupporting
confidence: 71%
“…This transcription factor regulates the promoter and mRNA expression of IGF2 in humans and mice. Interestingly, the phosphorylation of STAT3 decreased in MTE4-14 cells infected with CVB4 [89]. These observations suggest that the loss of STAT3 phosphorylation in TECs could result in a decrease in IGF2 P3 promoter activity, and consequently, in the decrease of IGF2 expression.…”
Section: Coxsackievirus B4 the Thymus Gland And Type 1 Diabetesmentioning
confidence: 80%
“…The effect of CV-B4 in utero infection of the thymus on transcription factors and autoantigens expression, especially in TECs for which we could not prove the infection, might be indirect via epigenetic regulation [ 60 , 61 , 62 ]. Similar to our results, a downregulation of IGF2 expression in enriched TECs of mice following CV-B4 infection was observed, despite the absence of a proof of infection of those cells, which raises this hypothesis [ 38 ]. Indeed, demethylation of DNA was one of the suggested mechanisms of epigenetic control of autoantigens expression in murine mTECs, such as Igf2 [ 63 ].…”
Section: Discussionsupporting
confidence: 90%
“…Nevertheless, we failed to detect CV-B4 RNA in the thymus of fetuses harvested 48 h after inoculation (data not shown). In a recent study, viral RNA was detected only in the pancreas of CV-B4-inoculated Swiss mice, but not in sorted total thymic cells isolated after enzymatic digestion [ 38 ].…”
Section: Discussionmentioning
confidence: 99%
“…The long-term presence of viral RNA in the pancreas of CD-1 mice infected with CVB4 E2 was associated with chronic islet inflammation, increased islet autoantibodies and development of diabetes mellitus 6–12 months after infection 29 . The infection of Swiss albino mice with CVB4 alters Igf2 expression in TECs, which leads to a decrease in pro-IGF2 protein 119 . Furthermore, deficient Igf2 expression in the thymus has been implicated in the development of autoimmune diabetes mellitus in BBDP rats 120 .…”
Section: Experimental Evidence For Cvb Persistencementioning
confidence: 99%