title: Chromatin disruption in the promoter of bovine leukemia virus during transcriptional activation.
abstract: Bovine leukemia virus expression relies on its chromatin organization after integration into the host cell genome. Proviral latency, which results from transcriptional repression in vivo, represents a viral strategy to escape the host immune system and likely allows for tumor progression. Here, we discriminated two types of latency: an easily reactivable latent state of the YR2 provirus and a 'locked' latent state of the L267 provirus. The defective YR2 provirus was characterized by the presence of nuclease hypersensitive sites at the U3/R junction and in the R/U5 region of the 5'-long terminal repeat (5'-LTR), whereas the L267 provirus displayed a closed chromatin configuration at the U3/R junction. Reactivation of viral expression in YR2 cells by the phorbol 12-myristate 13-acetate (PMA) plus ionomycin combination was accompanied by a rapid but transient chromatin remodeling in the 5'-LTR, leading to an increased PU.1 and USF-1/USF-2 recruitment in vivo sustained by PMA/ionomycin-mediated USF phosphorylation. In contrast, viral expression was not reactivated by PMA/ionomycin in L267 cells, because the 5'-LTR U3/R region remained inaccessible to nucleases and hypermethylated at CpG dinucleotides. Remarkably, we elucidated the BLV 5'-LTR chromatin organization in PBMCs isolated from BLV-infected cows, thereby depicting the virus hiding in vivo in its natural host.
authors: Laboratoire de Virologie Moléculaire, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Rue des Profs Jeener et Brachet 12, 6041 Gosselies, Belgium.
authors: Laurence
authors: L
authors: Colin
authors: Ann
authors: A
authors: Dekoninck
authors: Michal
authors: M
authors: Reichert
authors: Miriam
authors: M
authors: Calao
authors: Makram
authors: M
authors: Merimi
authors: Anne
authors: A
authors: Van den Broeke
authors: Valérie
authors: V
authors: Vierendeel
authors: Yvette
authors: Y
authors: Cleuter
authors: Arsène
authors: A
authors: Burny
authors: Olivier
authors: O
authors: Rohr
authors: Carine
authors: C
authors: Van Lint
mesh_terms: D000818:Animals; D001665:Binding Sites; D061207:Calcium Ionophores / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry* / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly; D015759:Ionomycin / Q000494:pharmacology; D001909:Leukemia Virus, Bovine / Q000235:genetics*; D009707:Nucleosomes / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D020079:Terminal Repeat Sequences; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D061207:Calcium Ionophores; D002843:Chromatin; D015759:Ionomycin; D009707:Nucleosomes; D011518:Proto-Oncogene Proteins; D016329:Sp1 Transcription Factor; D013755:Tetradecanoylphorbol Acetate; D015534:Trans-Activators; D051720:Upstream Stimulatory Factors; D000099232:Proto-Oncogene Protein Spi-1