scholarly journals Implication of the cellular factor CTCF in the regulation of Bovine Leukemia Virus latency and tridimensional chromatin organization

2021 ◽  
Author(s):  
Anthony Rodari ◽  
Maxime Bellefroid ◽  
Mathilde Galais ◽  
Peter H.L. Krijger ◽  
Lorena Nestola ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Promoter Activity ◽  
Integration Site ◽  
Leukemia Virus ◽  
Critical Role ◽  
Chromatin Organization ◽  
Ctcf Binding ◽  
Virus Latency ◽  
Ltr Promoter

ABSTRACTBovine Leukemia Virus (BLV)-induced tumoral development is a multifactorial phenomenon which remains largely unelucidated. Here, we highlighted the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the tridimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the BLV provirus. Next, we showed a critical role for CTCF in delimitating the epigenetic landscape along the BLV provirus as well as to repress the 5’Long Terminal Repeat (LTR) promoter activity, thereby contributing to viral latency, while favoring the 3’LTR promoter activity. Finally, we demonstrated that BLV integration deregulated host cellular 3D chromatin organization through the formation of abnormal viral/host chromatin loops. Altogether, our results highlight CTCF as a new critical effector of BLV transcriptional regulation and BLV-induced physiopathology.

scholarly journals PRMT5 Is Required for Bovine Leukemia Virus Infection In Vivo and Regulates BLV Gene Expression, Syncytium Formation, and Glycosylation In Vitro

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 650 ◽  
Author(s):  
Wlaa Assi ◽  
Tomoya Hirose ◽  
Satoshi Wada ◽  
Ryosuke Matsuura ◽  
Shin-nosuke Takeshima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Molecule ◽  
Bovine Leukemia Virus ◽  
Proviral Load ◽  
Leukemia Virus ◽  
Syncytium Formation ◽  
High Proviral Load

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle and is closely related to human T-cell leukemia viruses. We investigated the role of a new host protein, PRMT5, in BLV infection. We found that PRMT5 is overexpressed only in BLV-infected cattle with a high proviral load, but not in those with a low proviral load. Furthermore, this upregulation continued to the lymphoma stage. PRMT5 expression was upregulated in response to experimental BLV infection; moreover, PRMT5 upregulation began in an early stage of BLV infection rather than after a long period of proviral latency. Second, siRNA-mediated PRMT5 knockdown enhanced BLV gene expression at the transcript and protein levels. Additionally, a selective small-molecule inhibitor of PRMT5 (CMP5) enhanced BLV gene expression. Interestingly, CMP5 treatment, but not siRNA knockdown, altered the gp51 glycosylation pattern and increased the molecular weight of gp51, thereby decreasing BLV-induced syncytium formation. This was supported by the observation that CMP5 treatment enhanced the formation of the complex type of N-glycan more than the high mannose type. In conclusion, PRMT5 overexpression is related to the development of BLV infection with a high proviral load and lymphoma stage and PRMT5 inhibition enhances BLV gene expression. This is the first study to investigate the role of PRMT5 in BLV infection in vivo and in vitro and to reveal a novel function for a small-molecule compound in BLV-gp51 glycosylation processing.

In vivo transcription of bovine leukemia virus and bovine immunodeficiency-like virus

2003 ◽  
Vol 97 (2) ◽  
pp. 81-87 ◽  
Author(s):  
Donglai Wu ◽  
Kenji Murakami ◽  
Akira Morooka ◽  
Hong Jin ◽  
Yasuo Inoshima ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Leukemia Virus

scholarly journals Discordance between Bovine Leukemia Virus Tax Immortalization In Vitro and Oncogenicity In Vivo

2000 ◽  
Vol 74 (21) ◽  
pp. 9895-9902 ◽  
Author(s):  
Jean-Claude Twizere ◽  
Pierre Kerkhofs ◽  
Arsène Burny ◽  
Daniel Portetelle ◽  
Richard Kettmann ◽  
...  
Keyword(s):  
Viral Replication ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Wild Type Virus ◽  
Target Cells ◽  
Phosphorylation Sites ◽  
Primary Cells ◽  
Wild Type

ABSTRACT Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second function, immortalization of primary cells in vitro. These activities of Tax can be dissociated on the basis of point mutations within specific regions of the protein. For example, mutation of the phosphorylation sites at serines 106 and 293 abrogates immortalization potential in vitro but maintains transcriptional activity. This type of mutant is thus particularly useful for unraveling the role of Tax immortalization activity during leukemogenesis independently of viral replication. In this report, we describe the biological properties of BLV recombinant proviruses mutated in the Tax phosphorylation sites (BLVTax106+293). Titration of the proviral loads by semiquantitative PCR revealed that the BLV mutants propagated at wild-type levels in vivo. Furthermore, two animals (sheep 480 and 296) infected with BLVTax106+293 developed leukemia or lymphosarcoma after 16 and 36 months, respectively. These periods of time are within the normal range of latencies preceding the onset of pathogenesis induced by wild-type viruses. The phenotype of the mutant-infected cells was characteristic of a B lymphocyte (immunoglobulin M positive) expressing CD11b and CD5 (except at the final stage for the latter marker), a pattern that is typical of wild-type virus-infected target cells. Interestingly, the transformed B lymphocytes from sheep 480 also coexpressed the CD8 marker, a phenotype rarely observed in tumor biopsies from chronic lymphocytic leukemia patients. Finally, direct sequencing of the tax gene demonstrated that the leukemic cells did not harbor revertant proviruses. We conclude that viruses expressing a Tax mutant unable to transform primary cells in culture are still pathogenic in the sheep animal model. Our data thus provide a clear example of the discordant conclusions that can be drawn from in vitro immortalization assays and in vivo experiments. These observations could be of interest for other systems, such as the related human T-cell leukemia virus type 1, which currently lack animal models allowing the study of the leukemogenic process.

Bovine leukemia virus gene expression in vivo.

1992 ◽  
Vol 66 (10) ◽  
pp. 6223-6225 ◽  
Author(s):  
L Haas ◽  
T Divers ◽  
J W Casey
Keyword(s):  
Gene Expression ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Virus Gene ◽  
Virus Gene Expression

Development of aerial and belowground tubers in potato is governed by photoperiod and epigenetic mechanism

2021 ◽  
Author(s):  
Kirtikumar R Kondhare ◽  
Amit Kumar ◽  
Nikita S Patil ◽  
Nilam N Malankar ◽  
Kishan Saha ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Developmental Plasticity ◽  
Integration Site ◽  
Leukemia Virus ◽  
Polycomb Group ◽  
Epigenetic Mechanism ◽  
Growth Responses ◽  
Short Day

Abstract Plants exhibit diverse developmental plasticity and modulate growth responses under various environmental conditions. Potato (Solanum tuberosum), a modified stem and an important food crop, serves as a substantial portion of the world’s subsistence food supply. In the past two decades, crucial molecular signals have been identified that govern the tuberization (potato development) mechanism. Interestingly, microRNA156 overexpression in potato provided the first evidence for induction of profuse aerial stolons and tubers from axillary-meristems under short-day photoperiod. A similar phenotype was noticed for overexpression of epigenetic modifiers - MUTICOPY SUPRESSOR OF IRA1 (StMSI1) or ENAHNCER OF ZESTE 2 (StE[z]2), and knockdown of B-CELL SPECIFIC MOLONEY MURINE LEUKEMIA VIRUS INTEGRATION SITE 1 (StBMI1). This striking phenotype represents a classic example of modulation of plant architecture and developmental plasticity. Differentiation of a stolon to a tuber or a shoot under in vitro or in vivo conditions symbolizes another example of organ level plasticity and dual fate acquisition in potato. Stolon-to-tuber transition is governed by short-day photoperiod, mobile RNAs/proteins, phytohormones, a plethora of small RNAs and their targets. Recent studies show that polycomb group proteins control microRNA156, phytohormone metabolism/transport/signalling, and key tuberization genes through histone modifications to govern tuber development. Our comparative analysis of differentially expressed genes between the overexpression lines of StMSI1, StBEL5 (BEL1-LIKE transcription factor) and POTH15 (POTATO HOMEOBOX 15 transcription factor) revealed >1000 common genes, indicative of a mutual gene regulatory network potentially involved in the formation of aerial and belowground tubers. In this review, in addition to key tuberization factors, we highlight the role of photoperiod and epigenetic mechanism that regulates the development of aerial and belowground tubers in potato.

scholarly journals Latency of Viral Expression In Vivo Is Not Related to CpG Methylation in the U3 Region and Part of the R Region of the Long Terminal Repeat of Bovine Leukemia Virus

2003 ◽  
Vol 77 (7) ◽  
pp. 4423-4430 ◽  
Author(s):  
Shigeru Tajima ◽  
Masako Tsukamoto ◽  
Yoko Aida
Keyword(s):  
Long Terminal Repeat ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Cpg Methylation ◽  
Terminal Repeat ◽  
Luciferase Reporter ◽  
Reporter System ◽  
Methylation Of Dna ◽  
R Region

ABSTRACT Bovine leukemia virus (BLV) is silent in most cells detectable in vivo, and the repression of its expression allows BLV to evade the host's immune response. In this study, we examined whether CpG methylation of DNA might be involved in the regulation of the expression of BLV in vivo. To investigate the effects of CpG methylation on the activity of the long terminal repeat (LTR) of BLV, we measured the transactivation activity of this region after treatment with the CpG methyltransferase SssI by using a luciferase reporter system. The activity of methylated LTR was significantly lower than that of nonmethylated LTR. Therefore, we examined the extent of CpG methylation of the U3 region and part of the R region of the LTR in BLV-infected cattle and in experimentally BLV-infected sheep at various clinical stages by the bisulfite genomic sequencing method. We detected no or minimal CpG methylation at all stages examined in cattle and sheep, and our results indicate that CpG methylation probably does not participate in the silencing of BLV in vivo.

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