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Role of the cellular factor UHRF1 in the transcriptional regulation of Bovine Leukemia Virus and Human T-lymphotropic Virus type 1

par Plant, Estelle
Président du jury Vanhamme, Luc
Promoteur Van Lint, Carine
Publication Non publié, 2023-04-18

Thèse de doctorat

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Résumé :

Bovine Leukemia Virus (BLV) and Human T-Lymphotropic Virus type I (HTLV-1) are two oncogenic retroviruses characterized by viral latency, thereby allowing escape from the host immune surveillance and the development of BLV- and HTLV-1-associated diseases. In this PhD thesis, we demonstrated for the first time the role of the cellular factor UHRF1 (Ubiquitin-like with PHD and RING Finger domains 1) in the transcriptional repression of BLV and HTLV-1. We showed the in vitro binding and in vivo recruitment of UHRF1 to the BLV and HTLV-1 transcriptional promoters located in the viral 5’ Long Terminal Repeat (5’LTR). We demonstrated the repressive role of UHRF1 in BLV and HTLV-1 gene expression in both basal and transactivated conditions using transient transfection assays. Moreover, we showed that UHRF1 epigenetically repressed the HTLV-1 5’LTR using RNA interference and that UHRF1 interacted with the HTLV-1 Tax transactivator. Finally, our results using primary cells from HTLV-1-infected individuals suggested the involvement of UHRF1 in the tumoral development observed in the HTLV-1-infected individuals. In conclusion, this PhD thesis provides a better understanding of BLV and HTLV-1 transcriptional regulations and offers new perspectives for developing innovative therapeutic strategies against BLV and HTLV-1 infections and their associated diseases.