scholarly journals An Interferon Regulatory Factor Binding Site in the U5 Region of the Bovine Leukemia Virus Long Terminal Repeat Stimulates Tax-Independent Gene Expression

1998 ◽  
Vol 72 (7) ◽  
pp. 5526-5534 ◽  
Author(s):  
Véronique Kiermer ◽  
Carine Van Lint ◽  
Delphine Briclet ◽  
Caroline Vanhulle ◽  
Richard Kettmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Terminal Repeat ◽  
Binding Site ◽  
Bovine Leukemia Virus ◽  
Transcription Initiation ◽  
Leukemia Virus ◽  
Viral Gene Expression ◽  
Terminal Repeat ◽  
Viral Gene ◽  
Enhancer Activity

ABSTRACT Bovine leukemia virus (BLV) replication is controlled by bothcis- and trans-acting elements. The virus-encoded transactivator, Tax, is necessary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequences that control Tax-independent transcription must play an important role in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gene expression directed by the BLV promoter. R-U5 was also stimulatory when inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5′ half of U5 is principally responsible for the stimulation. This element exhibited enhancer activity when inserted upstream or downstream from the herpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expression. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication.

scholarly journals Upstream Stimulatory Factors Binding to an E Box Motif in the R Region of the Bovine Leukemia Virus Long Terminal Repeat Stimulates Viral Gene Expression

2001 ◽  
Vol 277 (11) ◽  
pp. 8775-8789 ◽  
Author(s):  
Claire Calomme ◽  
Thi Liên-Anh Nguyên ◽  
Yvan de Launoit ◽  
Véronique Kiermer ◽  
Louis Droogmans ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Terminal Repeat ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Gene Expression ◽  
Terminal Repeat ◽  
Viral Gene ◽  
E Box ◽  
R Region

scholarly journals Identification and characterization of a PU.1/Spi-B binding site in the bovine leukemia virus long terminal repeat

Oncogene ◽  
2003 ◽  
Vol 22 (19) ◽  
pp. 2882-2896 ◽  
Author(s):  
Ann Dekoninck ◽  
Claire Calomme ◽  
Séverine Nizet ◽  
Yvan de Launoit ◽  
Arsène Burny ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Binding Site ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Terminal Repeat ◽  
Identification And Characterization

Binding of a cellular protein to the gibbon ape leukemia virus enhancer

1987 ◽  
Vol 7 (8) ◽  
pp. 2735-2744
Author(s):  
J P Quinn ◽  
N Holbrook ◽  
D Levens
Keyword(s):  
Long Terminal Repeat ◽  
Specific Binding ◽  
Leukemia Virus ◽  
Cellular Protein ◽  
Terminal Repeat ◽  
Enhancer Activity ◽  
Repeated Element ◽  
Gibbon Ape Leukemia Virus

The gibbon ape leukemia virus (GALV) contains enhancer activity within its long terminal repeat. In the GALV Seato strain this activity resides in a 48-base-pair (bp) repeated element. We demonstrate the existence of a cellular protein which binds in this region of the Seato strain. A sensitive method for enriching protein-DNA complexes from crude extracts coupled with exonuclease and DNase footprint analysis revealed the specific binding of this protein to a 21-bp region within each repeated element. A 22-bp oligonucleotide fragment defined solely by the 21-bp footprint binds a protein in vitro and displays enhancer activity in vivo, suggesting that this protein is a major determinant of GALV enhancer activity. The protein is present in three cell lines which are positive for enhancer activity and is not detected in Jurkat cells, which are negative for enhancer activity. Only GALV long-terminal-repeat variants which support high levels of enhancer activity in vivo compete with this protein for specific binding in vitro, suggesting a potential role for the protein in determining enhancer activity. This protein binding is not inhibited by competition with heterologous retroviral enhancers, demonstrating that it is not a ubiquitous retroviral enhancer binding protein.

scholarly journals Overlapping CRE and E Box Motifs in the Enhancer Sequences of the Bovine Leukemia Virus 5′ Long Terminal Repeat Are Critical for Basal and Acetylation-Dependent Transcriptional Activity of the Viral Promoter: Implications for Viral Latency

2004 ◽  
Vol 78 (24) ◽  
pp. 13848-13864 ◽  
Author(s):  
Claire Calomme ◽  
Ann Dekoninck ◽  
Séverine Nizet ◽  
Emmanuelle Adam ◽  
Thi Liên-Anh Nguyên ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Bovine Leukemia Virus ◽  
Transcriptional Repression ◽  
Trichostatin A ◽  
Leukemia Virus ◽  
Viral Latency ◽  
Terminal Repeat ◽  
Binding Studies ◽  
Viral Promoter ◽  
E Box

ABSTRACT Bovine leukemia virus (BLV) infection is characterized by viral latency in a large proportion of cells containing an integrated provirus. In this study, we postulated that mechanisms directing the recruitment of deacetylases to the BLV 5′ long terminal repeat (LTR) could explain the transcriptional repression of viral expression in vivo. Accordingly, we showed that BLV promoter activity was induced by several deacetylase inhibitors (such as trichostatin A [TSA]) in the context of episomal LTR constructs and in the context of an integrated BLV provirus. Moreover, treatment of BLV-infected cells with TSA increased H4 acetylation at the viral promoter, showing a close correlation between the level of histone acetylation and transcriptional activation of the BLV LTR. Among the known cis-regulatory DNA elements located in the 5′ LTR, three E box motifs overlapping cyclic AMP responsive elements (CREs) in U3 were shown to be involved in transcriptional repression of BLV basal gene expression. Importantly, the combined mutations of these three E box motifs markedly reduced the inducibility of the BLV promoter by TSA. E boxes are susceptible to recognition by transcriptional repressors such as Max-Mad-mSin3 complexes that repress transcription by recruiting deacetylases. However, our in vitro binding studies failed to reveal the presence of Mad-Max proteins in the BLV LTR E box-specific complexes. Remarkably, TSA increased the occupancy of the CREs by CREB/ATF. Therefore, we postulated that the E box-specific complexes exerted their negative cooperative effect on BLV transcription by steric hindrance with the activators CREB/ATF and/or their transcriptional coactivators possessing acetyltransferase activities. Our results thus suggest that the overlapping CRE and E box elements in the BLV LTR were selected during evolution as a novel strategy for BLV to allow better silencing of viral transcription and to escape from the host immune response.

Bovine leukemia virus long terminal repeat: a cell type-specific promoter

Science ◽  
1985 ◽  
Vol 227 (4684) ◽  
pp. 317-320 ◽  
Author(s):  
D Derse ◽  
S. Caradonna ◽  
J. Casey
Keyword(s):  
Long Terminal Repeat ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Terminal Repeat ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Extensive epitranscriptomic methylation of A and C residues on murine leukemia virus transcripts enhances viral gene expression

2019 ◽  
Author(s):  
David G. Courtney ◽  
Andrea Chalem ◽  
Hal P. Bogerd ◽  
Brittany A. Law ◽  
Edward M. Kennedy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Replication ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Positive Role ◽  
Viral Rnas ◽  
Order Of Magnitude ◽  
Murine Leukemia

AbstractWhile it has been known for several years that viral RNAs are subject to the addition of several distinct covalent modifications to individual nucleotides, collectively referred to as epitranscriptomic modifications, the effect of these editing events on viral gene expression has been controversial. Here, we report the purification of murine leukemia virus (MLV) genomic RNA to homogeneity and show that this viral RNA contains levels ofN6-methyladenosine (m6A), 5-methylcytosine (m5C) and 2’O-methylated (Nm) ribonucleotides that are an order of magnitude higher than detected on bulk cellular mRNAs. Mapping of m6A and m5C residues on MLV transcripts identified multiple discrete editing sites and allowed the construction of MLV variants bearing silent mutations that removed a subset of these sites. Analysis of the replication potential of these mutants revealed a modest but significant attenuation in viral replication in 3T3 cells in culture. Consistent with a positive role for m6A and m5C in viral replication, we also demonstrate that overexpression of the key m6A reader protein YTHDF2 enhances MLV replication, while downregulation of the m5C writer NSUN2 inhibits MLV replication.ImportanceThe data presented in this manuscript demonstrate that MLV RNAs bear an exceptionally high level of the epitranscriptomic modifications m6A, m5C and Nm, thus suggesting that these each facilitate some aspect of the viral replication cycle. Consistent with this hypothesis, we demonstrate that mutational removal of a subset of these m6A or m5C modifications from MLV transcripts inhibits MLV replication incisand a similar result was also observed upon manipulation of the level of expression of key cellular epitranscriptomic cofactors intrans. Together, these results argue that the addition of several different epitranscriptomic modifications to viral transcripts stimulates viral gene expression and suggest that MLV has therefore evolved to maximize the level of these modifications that are added to viral RNAs.

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