scholarly journals Yin Yang 1 is a potent activator of human T lymphotropic virus type 1 LTR-driven gene expression via RNA binding

2020 ◽  
Vol 117 (31) ◽  
pp. 18701-18710
Author(s):  
Gary Z. Wang ◽  
Stephen P. Goff
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Virus Type ◽  
Dna Sequences ◽  
Rna Binding ◽  
T Lymphotropic Virus ◽  
Yin Yang 1 ◽  
Yin Yang ◽  
R Region

Yin Yang 1 (YY1) is a DNA-binding transcription factor that either activates or represses gene expression. YY1 has previously been implicated in the transcriptional silencing of many retroviruses by binding to DNA sequences in the U3 region of the viral long terminal repeat (LTR). We here show that YY1 overexpression leads to profound activation, rather than repression, of human T lymphotropic virus type 1 (HTLV-1) expression, while YY1 down-regulation reduces HTLV-1 expression. The YY1 responsive element mapped not to YY1 DNA-binding sites in the HTLV-1 LTR but to the R region. The HTLV-1 R sequence alone is sufficient to provide YY1 responsiveness to a nonresponsive promoter, but only in the sense orientation and only when included as part of the mRNA. YY1 binds to the R region of HTLV-1 RNA in vitro and in vivo, leading to increased transcription initiation and elongation. The findings indicate that YY1 is a potent transactivator of HTLV-1 gene expression acting via binding viral RNA, rather than DNA.

scholarly journals Human T-Lymphotropic Virus Type 1 p30IIRegulates Gene Transcription by Binding CREB Binding Protein/p300

2001 ◽  
Vol 75 (20) ◽  
pp. 9885-9895 ◽  
Author(s):  
Weiqing Zhang ◽  
John W. Nisbet ◽  
Bjorn Albrecht ◽  
Wei Ding ◽  
Fatah Kashanchi ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Gene Transcription ◽  
Virus Type ◽  
Binding Protein ◽  
Creb Binding Protein ◽  
Cell Nuclei ◽  
T Lymphotropic Virus ◽  
P300 Binding

ABSTRACT The highly conserved coadapters CREB binding protein (CBP) and p300 form complexes with CREB as well as other DNA binding transcription factors to modulate chromatin remodeling and thus transcription. Human T-lymphotropic virus type 1 (HTLV-1) transcription is controlled, in part, by the CREB/ATF family of transcription factors which bind promoter sequences and function as complexes with the viral oncogenic protein Tax. We have reported that the nuclear localizing protein p30II of HTLV-1 functions as a transcription factor, differentially modulates CREB-responsive promoters, and is critical for maintenance of proviral loads in rabbits. In this study, we tested whether p30IIdirectly interacts with CBP/p300 to modulate gene transcription. Gal4(BD)-p30II-mediated transactivation was enhanced following exogenous expression of p300 and was competitively repressed by the p300 binding protein, adenovirus E1A, and E1ACR2 (mutated for retinoblastoma binding but retaining p300 binding). In contrast, E1ACR1 (mutated for p300 binding) failed to alter Gal4(BD)-p30II-mediated transactivation. In addition, Gal4(BD)-p30II-mediated transactivation was competitively inhibited by the cotransfection of CMV-p30II-HA and CMV-Tax but could be rescued by exogenous p300. Importantly, we demonstrate that p30II colocalizes with p300 in cell nuclei and directly binds to CBP/p300 in cells. Deletion mutants of CBP/p300 were used to localize the site critical for binding p30II to a highly conserved KIX region. DNA binding assays confirmed the interference of p30II with the assembly of CREB-Tax-p300/CBP multiprotein complexes on 21-bp repeat oligonucleotides in vitro. Collectively, our results demonstrate that CBP/p300 is a cellular protein target for HTLV-1 p30II and mediates its transcriptional effects in vivo.

scholarly journals Human T-Lymphotropic Virus Type 1 p30IIFunctions as a Transcription Factor and Differentially Modulates CREB-Responsive Promoters

2000 ◽  
Vol 74 (23) ◽  
pp. 11270-11277 ◽  
Author(s):  
Weiqing Zhang ◽  
John W. Nisbet ◽  
Joshua T. Bartoe ◽  
Wei Ding ◽  
Michael D. Lairmore
Keyword(s):  
Dna Binding ◽  
Fusion Protein ◽  
Reporter Gene ◽  
Virus Type ◽  
Mammalian Cells ◽  
Gene Activity ◽  
Luciferase Reporter ◽  
Reporter Gene Activity ◽  
T Lymphotropic Virus

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1), a complex retrovirus, causes adult T-cell lymphoma/leukemia and is linked to a variety of immune-mediated disorders. The roles of proteins encoded in the pX open reading frame (ORF) II gene region in HTLV-1 replication or in mediating virus-associated diseases remain to be defined. A nucleus-localizing 30-kDa protein, p30II, encoded within pX ORF II has limited homology with the POU family of transcription factors. Recently, we reported that selected mutations in pX ORF II diminish the ability of HTLV-1 to maintain high viral loads in infected rabbits. Herein we have tested the transcriptional ability of p30II in mammalian cells by using yeast Gal4 fusion protein vectors and transfection of luciferase reporter genes driven by CREB-responsive promoters. p30II as a Gal4 DNA-binding domain (DBD) fusion protein transactivates Gal4-driven luciferase reporter gene activity up to 25-fold in 293 and HeLa-tat cells. We confirmed nuclear localization of p30II and demonstrate dose-dependent binding of p30II-Gal4(DBD) to Gal4 DNA-binding sites. The transcriptional activity of p30II-Gal4(DBD) was independent of TATA box flanking sequences, as shown by using two different Gal4 reporter systems. Studies of selected p30II mutants indicated that domains that mediate transcription are restricted to a central core region of the protein between amino acids 62 and 220. Transfection of a p30II-expressing plasmid repressed cellular CRE-driven reporter gene activity, with or without Tax expression. In contrast, p30II at lower concentrations enhanced HTLV-1 long terminal repeat-driven reporter gene activity independent of Tax expression. These data are the first to demonstrate a transcriptional function for p30II and suggest a mechanism by which this nuclear protein may influence HTLV-1 replication or cellular gene expression in vivo.

scholarly journals RelA-Associated Inhibitor Blocks Transcription of Human Immunodeficiency Virus Type 1 by Inhibiting NF-κB and Sp1 Actions

2002 ◽  
Vol 76 (16) ◽  
pp. 8019-8030 ◽  
Author(s):  
Norio Takada ◽  
Takaomi Sanda ◽  
Hiroshi Okamoto ◽  
Jian-Ping Yang ◽  
Kaori Asamitsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
Dna Binding ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT RelA-associated inhibitor (RAI) is an inhibitor of nuclear factor κB (NF-κB) newly identified by yeast two-hybrid screen as an interacting protein of the p65 (RelA) subunit. In this study, we attempted to examine the effect of RAI on transcription and replication of human immunodeficiency virus type 1 (HIV-1). We found that RAI inhibited gene expression from the HIV-1 long terminal repeat (LTR) even at the basal level. Upon in vitro DNA-binding reactions, RAI could directly block the DNA-binding of p65 subunit of NF-κB but not that of the p50 subunit or AP1. We found that RAI could also inhibit the DNA-binding of Sp1 and thus inhibit the basal HIV-1 promoter activity. We further examined the effects of RAI on Sp1 and found that RAI colocalizes with Sp1 in the nucleus and interacts with Sp1 in vitro and in vivo. Moreover, we found that RAI efficiently blocked the HIV-1 replication when cotransfected with a full-length HIV-1 clone. These findings indicate that RAI acts as an efficient inhibitor of HIV-1 gene expression in which both NF-κB and Sp1 play major roles.

scholarly journals The immune control and cell-to-cell spread of human T-lymphotropic virus type 1

2003 ◽  
Vol 84 (12) ◽  
pp. 3177-3189 ◽  
Author(s):  
Charles R. M. Bangham
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Virus Type ◽  
Cell Function ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Cell Contact ◽  
T Lymphotropic Virus ◽  
Cell Spread

Human T-lymphotropic virus type 1 (HTLV-1) varies little in sequence compared with human immunodeficiency virus type 1 (HIV) and it is difficult to detect HTLV-1 mRNA, proteins or virions in fresh blood. But the strong and chronically activated T cell response to the virus indicates that HTLV-1 proteins are expressed persistently. It now appears that the efficiency of an individual's cytotoxic T cell (CTL) response to HTLV-1 is the chief single determinant of that person's provirus load, which can differ between HTLV-1-infected people by more than 10 000-fold. Progress is now being made towards defining this CTL ‘efficiency’ in terms of host genetics, T cell function, T cell gene expression and mathematical dynamics. Lymphocytes that are naturally infected with HTLV-1 do not produce enveloped extracellular virions in short-term culture and this has reinforced the erroneous conclusion that the virus is latent. But recent evidence shows that HTLV-1 can spread directly between lymphocytes across a specialized, virus-induced cell–cell contact – a ‘viral synapse’. Instead of making extracellular virions, HTLV-1 uses the mobility of the host cell to spread within and between hosts. In this review the evidence is summarized on the persistent gene expression of HTLV-1 in vivo, the role of the immune system in protection and pathogenesis in HTLV-1 infection, and the mechanism of cell-to-cell spread of HTLV-1.

Drug Targets in Human T-Lymphotropic Virus Type 1 (HTLV-1) Infection

2009 ◽  
Vol 9 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Peter Boross ◽  
Peter Bagossi ◽  
Irene Weber ◽  
Jozsef Tozser
Keyword(s):  
Virus Type ◽  
Drug Targets ◽  
T Lymphotropic Virus
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