Fiche publication
Date publication
mai 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MARCAIS Ambroise
Tous les auteurs :
Rosewick N, Durkin K, Artesi M, Marçais A, Hahaut V, Griebel P, Arsic N, Avettand-Fenoel V, Burny A, Charlier C, Hermine O, Georges M, Van den Broeke A
Lien Pubmed
Résumé
Human T-cell leukaemia virus type-1 (HTLV-1) and bovine leukaemia virus (BLV) infect T- and B-lymphocytes, respectively, provoking a polyclonal expansion that will evolve into an aggressive monoclonal leukaemia in ∼5% of individuals following a protracted latency period. It is generally assumed that early oncogenic changes are largely dependent on virus-encoded products, especially TAX and HBZ, while progression to acute leukaemia/lymphoma involves somatic mutations, yet that both are independent of proviral integration site that has been found to be very variable between tumours. Here, we show that HTLV-1/BLV proviruses are integrated near cancer drivers which they affect either by provirus-dependent transcription termination or as a result of viral antisense RNA-dependent cis-perturbation. The same pattern is observed at polyclonal non-malignant stages, indicating that provirus-dependent host gene perturbation contributes to the initial selection of the multiple clones characterizing the asymptomatic stage, requiring additional alterations in the clone that will evolve into full-blown leukaemia/lymphoma.
Mots clés
Adult, Animals, Carcinogenesis, genetics, Cattle, Female, Genome, Host-Pathogen Interactions, genetics, Human T-lymphotropic virus 1, genetics, Humans, Leukemia, genetics, Leukemia Virus, Bovine, genetics, Male, Models, Biological, Proviruses, genetics, RNA, Antisense, metabolism, Sheep, Transcription, Genetic, Virus Integration, genetics
Référence
Nat Commun. 2017 05 23;8:15264
