Log in

Relevant bibliographies by topics / VPR-1 / Journal articles

To see the other types of publications on this topic, follow the link: VPR-1.

Journal articles on the topic 'VPR-1'

Author: Grafiati

Published: 4 June 2021

Last updated: 18 February 2022

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'VPR-1.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Anbalagan, Srivishnupriya, Elyse Cooper, Pat Klumper, Randy R. Simonson, and Ben M. Hause. "Whole genome analysis of epizootic hemorrhagic disease virus identified limited genome constellations and preferential reassortment." Journal of General Virology 95, no. 2 (2014): 434–41. http://dx.doi.org/10.1099/vir.0.059659-0.

Full text

Abstract:

Epizootic hemorrhagic disease virus (EHDV) is a Culicoides transmitted orbivirus that causes haemorrhagic disease in wild and domestic ruminants. A collection of 44 EHDV isolated from 2008 to 2012 was fully sequenced and analysed phylogenetically. Serotype 2 viruses were the dominant serotype all years except 2012 when serotype 6 viruses represented 63 % of the isolates. High genetic similarity (>94 % identity) between serotype 1 and 2 virus VP1, VP3, VP4, VP6, NS1, NS2 and NS3 segments prevented identification of reassortment events for these segments. Additionally, there was little geneti

APA, Harvard, Vancouver, ISO, and other styles

2

Jenkins, Yonchu, Owen Pornillos, Rebecca L. Rich, David G. Myszka, Wesley I. Sundquist, and Michael H. Malim. "Biochemical Analyses of the Interactions between Human Immunodeficiency Virus Type 1 Vpr and p6Gag." Journal of Virology 75, no. 21 (2001): 10537–42. http://dx.doi.org/10.1128/jvi.75.21.10537-10542.2001.

Full text

Abstract:

ABSTRACT The nonstructural human immunodeficiency virus type 1 Vpr protein is packaged into progeny virions at significant levels (∼200 copies/virion). Genetic analyses have demonstrated that efficient Vpr packaging is dependent upon a leucine-X-X-leucine-phenylalanine (LXXLF) motif located in the p6Gag domain of the structural Gag polyprotein. Recombinant proteins spanning full-length Vpr (Vpr1–97) or the amino-terminal 71 amino acids (Vpr1–71) formed specific complexes with recombinant p6 proteins in vitro. Complex formation required an intact LXXLF motif and exhibited an intrinsic dissociat

APA, Harvard, Vancouver, ISO, and other styles

3

Reis, Milena Ramos, Abrahão Alves de Oliveira Filho, Lilia Simone Urzedo Rodrigues, et al. "Involvement of Potassium Channels in Vasorelaxant Effect Induced byValeriana prionophyllaStandl. in Rat Mesenteric Artery." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/147670.

Full text

Abstract:

Assaysin vitroandin vivowere performed on extract from roots and leaves from theValeriana prionophyllaStandl. (VPR and VPF, resp.). In phenylephrine (1 μM) precontracted rings, VPR (0.01–300 μg/mL) induced a concentration-dependent relaxation (maximum response (MR) = 75.4 ± 4.0%, EC50= 5.97 (3.8–9.3)μg/mL,n=6]); this effect was significantly modified after removal of the endothelium (EC50= 39.6 (27.2–57.6)μg/mL,P<0.05). However, VPF-induced vasorelaxation was less effective compared to VPR. When rings were preincubated with L-NAME (100 μM) or indomethacin (10 μM), the endothelium-dependent

APA, Harvard, Vancouver, ISO, and other styles

4

Poon, Betty, and Irvin S. Y. Chen. "Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Enhances Expression from Unintegrated HIV-1 DNA." Journal of Virology 77, no. 7 (2003): 3962–72. http://dx.doi.org/10.1128/jvi.77.7.3962-3972.2003.

Full text

Abstract:

ABSTRACT Retroviral DNA synthesized prior to integration, termed unintegrated viral DNA, is classically believed to be transcriptionally inert and to serve only as a precursor to the transcriptionally active integrated proviral DNA form. However, it has recently been found to be expressed under some circumstances during human immunodeficiency virus type 1 (HIV-1) replication and may play a significant role in HIV-1 pathogenesis. HIV-1 Vpr is a virion-associated accessory protein that is critical for HIV-1 replication in nondividing cells and induces cell cycle arrest and apoptosis. We find tha

APA, Harvard, Vancouver, ISO, and other styles

5

Stark, Lesley A., and Ronald T. Hay. "Human Immunodeficiency Virus Type 1 (HIV-1) Viral Protein R (Vpr) Interacts with Lys-tRNA Synthetase: Implications for Priming of HIV-1 Reverse Transcription." Journal of Virology 72, no. 4 (1998): 3037–44. http://dx.doi.org/10.1128/jvi.72.4.3037-3044.1998.

Full text

Abstract:

ABSTRACT The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 96-amino-acid 14-kDa protein (viral protein R [Vpr]), which is produced late in the viral life cycle and is incorporated into the virion. Although Vpr is not required for viral replication in transformed cell lines and primary T lymphocytes, it is essential for productive infection of macrophages and monocytes and appears to be important for pathogenesis in vivo. To establish the role of Vpr in HIV-1 replication and pathogenesis, we have isolated cellular proteins with which Vpr interacts. By using the yeast two-hyb

APA, Harvard, Vancouver, ISO, and other styles

6

Yedavalli, Venkat S. R. K., Hsiu-Ming Shih, Yu-Ping Chiang, et al. "Human Immunodeficiency Virus Type 1 Vpr Interacts with Antiapoptotic Mitochondrial Protein HAX-1." Journal of Virology 79, no. 21 (2005): 13735–46. http://dx.doi.org/10.1128/jvi.79.21.13735-13746.2005.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and

APA, Harvard, Vancouver, ISO, and other styles

7

Ghosh, Souvik, Shyamal Kumar Paul, Mohammad Akram Hossain, Mohammed Mahbub Alam, Muzahed Uddin Ahmed, and Nobumichi Kobayashi. "Full genomic analyses of two human G2P[4] rotavirus strains detected in 2005: identification of a caprine-like VP3 gene." Journal of General Virology 92, no. 5 (2011): 1222–27. http://dx.doi.org/10.1099/vir.0.029868-0.

Full text

Abstract:

Although G2P[4] rotaviruses are common causes of infantile diarrhoea, to date only the full genomes of the prototype (strain DS-1) and another old strain, TB-Chen, have been analysed. We report here the full genomic analyses of two Bangladeshi G2P[4] strains, MMC6 and MMC88, detected in 2005. Both the strains exhibited a DS-1-like genotype constellation. Excluding the VP4 and VP7 genes, and except for VP3 of MMC88, the MMC strains were genetically more closely related to the contemporary G2P[4] and several non-G2P[4] human strains than the prototype G2P[4] strain. However, by phylogenetic anal

APA, Harvard, Vancouver, ISO, and other styles

8

Hrimech, Mohammed, Xiao-Jian Yao, François Bachand, Nicole Rougeau, and Éric A. Cohen. "Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Functions as an Immediate-Early Protein during HIV-1 Infection." Journal of Virology 73, no. 5 (1999): 4101–9. http://dx.doi.org/10.1128/jvi.73.5.4101-4109.1999.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Vpr is a virion-associated protein which facilitates HIV-1 infection of nondividing cells by contributing to the nuclear transport of the preintegration complex (PIC). Vpr was also shown to induce a cell cycle G2 arrest in infected proliferating cells that optimizes HIV-1 long terminal repeat (LTR)-directed gene expression and viral production. However, it is unclear whether this activity is mediated primarily early by virion-associated Vpr or alternatively late during infection when Vpr is de novo expressed. We report here that in the absen

APA, Harvard, Vancouver, ISO, and other styles

9

Romani, Bizhan, and Susan Engelbrecht. "Human immunodeficiency virus type 1 Vpr: functions and molecular interactions." Journal of General Virology 90, no. 8 (2009): 1795–805. http://dx.doi.org/10.1099/vir.0.011726-0.

Full text

Abstract:

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of cellular and viral proteins. The functions of many of these interactions in the pathogenesis of HIV-1 have been identified. Deletion of the vpr gene reduces the virulence of HIV-1 dramatically, indicating the importance of this protein for the virus. This review describes the current findings on several established functions of HIV-1 Vpr and some possible roles proposed for this protein. Because Vpr exploits cellular proteins and pathways to influence the biology of HIV-1,

APA, Harvard, Vancouver, ISO, and other styles

10

Roesch, Ferdinand, Léa Richard, Réjane Rua, Françoise Porrot, Nicoletta Casartelli, and Olivier Schwartz. "Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells." Journal of Virology 89, no. 23 (2015): 12118–30. http://dx.doi.org/10.1128/jvi.02098-15.

Full text

Abstract:

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr muta

APA, Harvard, Vancouver, ISO, and other styles

11

Iordanskiy, Sergey, Yuqi Zhao, Larisa Dubrovsky, et al. "Heat Shock Protein 70 Protects Cells from Cell Cycle Arrest and Apoptosis Induced by Human Immunodeficiency Virus Type 1 Viral Protein R." Journal of Virology 78, no. 18 (2004): 9697–704. http://dx.doi.org/10.1128/jvi.78.18.9697-9704.2004.

Full text

Abstract:

ABSTRACT Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is an accessory protein that plays an important role in viral pathogenesis. This pathogenic activity of Vpr is related in part to its capacity to induce cell cycle G2 arrest and apoptosis of target T cells. A screening for multicopy suppressors of these Vpr activities in fission yeast identified heat shock protein 70 (Hsp70) as a suppressor of Vpr-induced cell cycle arrest. Hsp70 is a member of a family of molecular chaperones involved in innate immunity and protection from environmental stress. In this report, we de

APA, Harvard, Vancouver, ISO, and other styles

12

Kino, Tomoshige, Alexander Gragerov, Olga Slobodskaya, Maria Tsopanomichalou, George P. Chrousos, and George N. Pavlakis. "Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators." Journal of Virology 76, no. 19 (2002): 9724–34. http://dx.doi.org/10.1128/jvi.76.19.9724-9734.2002.

Full text

Abstract:

ABSTRACT The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a promiscuous activator of viral and cellular promoters. We report that Vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to p/CAF or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting protein 1. Vpr forms a stable complex wit

APA, Harvard, Vancouver, ISO, and other styles

13

Murakami, Hironobu, Takehiro Suzuki, Kiyoto Tsuchiya, et al. "Protein Arginine N-methyltransferases 5 and 7 Promote HIV-1 Production." Viruses 12, no. 3 (2020): 355. http://dx.doi.org/10.3390/v12030355.

Full text

Abstract:

Current therapies for human immunodeficiency virus type 1 (HIV-1) do not completely eliminate viral reservoirs in cells, such as macrophages. The HIV-1 accessory protein viral protein R (Vpr) promotes virus production in macrophages, and the maintenance of Vpr is essential for HIV-1 replication in these reservoir cells. We identified two novel Vpr-binding proteins, i.e., protein arginine N-methyltransferases (PRMTs) 5 and 7, using human monocyte-derived macrophages (MDMs). Both proteins found to be important for prevention of Vpr degradation by the proteasome; in the context of PRMT5 and PRMT7

APA, Harvard, Vancouver, ISO, and other styles

14

Tan, Lindi, Elana Ehrlich, and Xiao-Fang Yu. "DDB1 and Cul4A Are Required for Human Immunodeficiency Virus Type 1 Vpr-Induced G2 Arrest." Journal of Virology 81, no. 19 (2007): 10822–30. http://dx.doi.org/10.1128/jvi.01380-07.

Full text

Abstract:

ABSTRACT Vpr-mediated induction of G2 cell cycle arrest has been postulated to be important for human immunodeficiency virus type 1 (HIV-1) replication, but the precise role of Vpr in this cell cycle arrest is unclear. In the present study, we have shown that HIV-1 Vpr interacts with damaged DNA binding protein 1 (DDB1) but not its partner DDB2. The interaction of Vpr with DDB1 was inhibited when DCAF1 (VprBP) expression was reduced by short interfering RNA (siRNA) treatment. The Vpr mutant (Q65R) that was defective for DCAF1 interaction also had a defect in DDB1 binding. However, Vpr binding

APA, Harvard, Vancouver, ISO, and other styles

15

Zeng, Carl Q. Y., Mary K. Estes, Annie Charpilienne, and Jean Cohen. "The N Terminus of Rotavirus VP2 Is Necessary for Encapsidation of VP1 and VP3." Journal of Virology 72, no. 1 (1998): 201–8. http://dx.doi.org/10.1128/jvi.72.1.201-208.1998.

Full text

Abstract:

ABSTRACT The innermost core of rotavirus is composed of VP2, which forms a protein layer that surrounds the two minor proteins VP1 and VP3, and the genome of 11 segments of double-stranded RNA. This inner core layer surrounded by VP6, the major capsid protein, constitutes double-layered particles that are transcriptionally active. Each gene encoding a structural protein of double-layered particles has been cloned into baculovirus recombinants and expressed in insect cells. Previously, we showed that coexpression of different combinations of the structural proteins of rotavirus double-layered p

APA, Harvard, Vancouver, ISO, and other styles

16

Zhao, Yuqi. "Yeast perspectives on HIV-1 VPR." Frontiers in Bioscience 5, no. 1 (2000): d905. http://dx.doi.org/10.2741/zhao.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Zhao, Yuqi. "Yeast perspectives on HIV-1 VPR." Frontiers in Bioscience 5, no. 3 (2000): d905–916. http://dx.doi.org/10.2741/a559.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Stewart, Sheila A., Betty Poon, Joo Y. Song, and Irvin S. Y. Chen. "Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation." Journal of Virology 74, no. 7 (2000): 3105–11. http://dx.doi.org/10.1128/jvi.74.7.3105-3111.2000.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion. Vpr induces cell cycle arrest at the G2/M phase of the cell cycle, and this arrest is followed by apoptosis. We examined the mechanism of Vpr-induced apoptosis and found that HIV-1 Vpr-induced apoptosis requires the activation of a number of cellular cysteinyl aspartate-specific proteases (caspases). We demonstrate that ectopic expression of anti-apoptotic viral proteins, which inhibit caspase activity, and addition of synthetic peptides, which represent caspase c

APA, Harvard, Vancouver, ISO, and other styles

19

Ardon, Orly, Erik S. Zimmerman, Joshua L. Andersen, Jason L. DeHart, Jana Blackett, and Vicente Planelles. "Induction of G2 Arrest and Binding to Cyclophilin A Are Independent Phenotypes of Human Immunodeficiency Virus Type 1 Vpr." Journal of Virology 80, no. 8 (2006): 3694–700. http://dx.doi.org/10.1128/jvi.80.8.3694-3700.2006.

Full text

Abstract:

ABSTRACT Cyclophilin A (CypA) is a member of a family of cellular proteins that share a peptidyl prolyl cis-trans isomerase (PPIase) activity. CypA was previously reported to be required for the biochemical stability and function (specifically, induction of G2 arrest) of the human immunodeficiency virus type 1 (HIV-1) protein R (Vpr). In the present study, we examine the role of the Vpr-CypA interaction on Vpr-induced G2 arrest. We find that Vpr coimmunoprecipitates with CypA and that this interaction is disrupted by substitution of proline-35 of Vpr as well as incubation with the CypA inhibit

APA, Harvard, Vancouver, ISO, and other styles

20

Benko, Zsigmond, Dong Liang, Emmanuel Agbottah, et al. "Anti-Vpr Activity of a Yeast Chaperone Protein." Journal of Virology 78, no. 20 (2004): 11016–29. http://dx.doi.org/10.1128/jvi.78.20.11016-11029.2004.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple effects on viral and host cellular activities during viral infection, including nuclear transport of the proviral integration complex, induction of cell cycle G2 arrest, and cell death. In this report, we show that a fission yeast chaperone protein Hsp16 inhibits HIV-1 by suppressing these Vpr activities. This protein was identified through three independent genome-wide screens for multicopy suppressors of each of the three Vpr activities. Consistent with the properties of a heat shock protein, heat shoc

APA, Harvard, Vancouver, ISO, and other styles

21

Lahouassa, Hichem, Marie-Lise Blondot, Lise Chauveau, et al. "HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages." Proceedings of the National Academy of Sciences 113, no. 19 (2016): 5311–16. http://dx.doi.org/10.1073/pnas.1600485113.

Full text

Abstract:

Viruses often interfere with the DNA damage response to better replicate in their hosts. The human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) protein has been reported to modulate the activity of the DNA repair structure-specific endonuclease subunit (SLX4) complex and to promote cell cycle arrest. Vpr also interferes with the base-excision repair pathway by antagonizing the uracil DNA glycosylase (Ung2) enzyme. Using an unbiased quantitative proteomic screen, we report that Vpr down-regulates helicase-like transcription factor (HLTF), a DNA translocase involved in the repair of da

APA, Harvard, Vancouver, ISO, and other styles

22

Gummuluru, Suryaram, and Michael Emerman. "Cell Cycle- and Vpr-Mediated Regulation of Human Immunodeficiency Virus Type 1 Expression in Primary and Transformed T-Cell Lines." Journal of Virology 73, no. 7 (1999): 5422–30. http://dx.doi.org/10.1128/jvi.73.7.5422-5430.1999.

Full text

Abstract:

ABSTRACT Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) transiently arrests cells in the G2 phase of the cell cycle and is a weak transcriptional transactivator. We found that Vpr increased HIV-1 long terminal repeat (LTR) activity in all cells examined but, when expressed at high levels, decreased HIV-1 LTR expression due to cytotoxic effects. Moreover, Vpr-mediated enhancement of HIV-1 LTR-driven transcription was observed in cycling primary human CD4+ T cells but not in terminally differentiated, noncycling primary human macrophages. In single-round infection experimen

APA, Harvard, Vancouver, ISO, and other styles

23

Conti, Lucia, Barbara Varano, M. Cristina Gauzzi, et al. "Impairment of Human Immunodeficiency Virus Type 1 (HIV-1) Entry into Jurkat T Cells by Constitutive Expression of the HIV-1 Vpr Protein: Role of CD4 Down-Modulation." Journal of Virology 74, no. 21 (2000): 10207–11. http://dx.doi.org/10.1128/jvi.74.21.10207-10211.2000.

Full text

Abstract:

ABSTRACT Jurkat T-cell clones, stably expressing the human immunodeficiency virus type 1 (HIV-1) Vpr protein, exhibited an impaired susceptibility to HIV-1 infection. A marked down-modulation of surface CD4 receptors was detected in Vpr-expressing clones with respect to control cells. Likewise, a reduced CD4 expression was also observed in parental Jurkat cells infected with wild-type but not with Vpr-mutant HIV-1. Notably, Vpr-expressing clones were fully susceptible to infection with a vesicular stomatitis virus G protein-pseudotyped HIV-1 virus, indicating that a block at the level of viral

APA, Harvard, Vancouver, ISO, and other styles

24

Langevin, Christelle, Priscilla Maidou-Peindara, Per Arne Aas, et al. "Human Immunodeficiency Virus Type 1 Vpr Modulates Cellular Expression of UNG2 via a Negative Transcriptional Effect." Journal of Virology 83, no. 19 (2009): 10256–63. http://dx.doi.org/10.1128/jvi.02654-08.

Full text

Abstract:

ABSTRACT It was recently reported that human immunodeficiency virus type 1 (HIV-1) Vpr induced the proteasomal degradation of the nuclear UNG2 enzyme for efficient virus replication. We confirm here that HIV-1 infection and Vpr expression reduce the level of endogenous UNG2, but this effect is not reverted by treatment with the proteasome inhibitor MG132. Moreover, this reduction is not mediated by Vpr binding to UNG2 and is independent of the Vpr-induced G2 arrest. Finally, we show that Vpr influences the UNG2 promoter without affecting UNG1 gene expression. These data indicate that the Vpr-i

APA, Harvard, Vancouver, ISO, and other styles

25

Schröfelbauer, Bärbel, Qin Yu, Samantha G. Zeitlin, and Nathaniel R. Landau. "Human Immunodeficiency Virus Type 1 Vpr Induces the Degradation of the UNG and SMUG Uracil-DNA Glycosylases." Journal of Virology 79, no. 17 (2005): 10978–87. http://dx.doi.org/10.1128/jvi.79.17.10978-10987.2005.

Full text

Abstract:

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr has previously been shown to bind to the cellular uracil DNA glycosylase UNG. We show here that the binding of Vpr to UNG and to the related enzyme SMUG induces their proteasomal degradation. UNG and SMUG were found to be encapsidated in Δvpr HIV-1 virions but were significantly less abundant in vpr + virions. Δvpr virions contained readily detectable uracil-DNA glycosylase enzymatic activity, while the activity was reduced to undetectable levels in vpr + virions. Consistent with proteasomal degradation, complexes t

APA, Harvard, Vancouver, ISO, and other styles

26

Yan, Junpeng, Ming-Chieh Shun, Yi Zhang, Caili Hao, and Jacek Skowronski. "HIV-1 Vpr counteracts HLTF-mediated restriction of HIV-1 infection in T cells." Proceedings of the National Academy of Sciences 116, no. 19 (2019): 9568–77. http://dx.doi.org/10.1073/pnas.1818401116.

Full text

Abstract:

Lentiviruses, including HIV-1, possess the ability to enter the nucleus through nuclear pore complexes and can infect interphase cells, including those actively replicating chromosomal DNA. Viral accessory proteins hijack host cell E3 enzymes to antagonize intrinsic defenses, and thereby provide a more permissive environment for virus replication. The HIV-1 Vpr accessory protein reprograms CRL4DCAF1 E3 to antagonize select postreplication DNA repair enzymes and activates the DNA damage checkpoint in the G2 cell cycle phase. However, little is known about the roles played by these Vpr targets i

APA, Harvard, Vancouver, ISO, and other styles

27

Fouchier, Ron A. M., Barbara E. Meyer, James H. M. Simon, et al. "Interaction of the Human Immunodeficiency Virus Type 1 Vpr Protein with the Nuclear Pore Complex." Journal of Virology 72, no. 7 (1998): 6004–13. http://dx.doi.org/10.1128/jvi.72.7.6004-6013.1998.

Full text

Abstract:

ABSTRACT The Vpr protein of human immunodeficiency virus type 1 (HIV-1) performs a number of functions that are associated with the nucleus. Vpr enhances the nuclear import of postentry viral nucleoprotein complexes, arrests proliferating cells in the G2phase of the cell cycle, and acts as a modest transcriptional activator. For this paper, we have investigated the nuclear import of Vpr. Although Vpr does not encode a sequence that is recognizable as a nuclear localization signal (NLS), Vpr functions as a transferable NLS both in somatic cells and inXenopus laevis oocytes. In certain contexts,

APA, Harvard, Vancouver, ISO, and other styles

28

Zhou, Yi, and Lee Ratner. "Phosphorylation of Human Immunodeficiency Virus Type 1 Vpr Regulates Cell Cycle Arrest." Journal of Virology 74, no. 14 (2000): 6520–27. http://dx.doi.org/10.1128/jvi.74.14.6520-6527.2000.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Vpr regulates nuclear transport of the viral preintegration complex, G2 cell cycle arrest, and transcriptional transactivation. We asked whether phosphorylation could affect Vpr activity. Vpr was found to be phosphorylated on serine residues in transiently transfected and infected cells. Residues 79, 94, and 96 were all found to be phosphorylated, as assessed by alanine mutations. Mutation of Ser-79 to Ala abrogated effects of Vpr on cell cycle progression, whereas mutation of Ser-94 and Ser-96 had no effect. Simultaneous mutation of all thr

APA, Harvard, Vancouver, ISO, and other styles

29

Lai, Maoyi, Erik S. Zimmerman, Vicente Planelles, and Junjie Chen. "Activation of the ATR Pathway by Human Immunodeficiency Virus Type 1 Vpr Involves Its Direct Binding to Chromatin In Vivo." Journal of Virology 79, no. 24 (2005): 15443–51. http://dx.doi.org/10.1128/jvi.79.24.15443-15451.2005.

Full text

Abstract:

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) protein Vpr (viral protein R) arrests cells in the G2 phase of the cell cycle, a process that requires activation of the ATR (ataxia-telangiectasia and Rad3-related) pathway. In this study we demonstrate that the expression of Vpr does not cause DNA double-strand breaks but rather induces ATR activation, as indicated by induction of Chk1 phosphorylation and the formation of γ-H2AX and 53BP1 nuclear foci. We define a C-terminal domain containing repeated H(F/S)RIG sequences required for Vpr-induced activation of ATR. Further investigation

APA, Harvard, Vancouver, ISO, and other styles

30

Bruce, James W., Megan Bracken, Edward Evans, Nathan Sherer, and Paul Ahlquist. "ZBTB2 represses HIV-1 transcription and is regulated by HIV-1 Vpr and cellular DNA damage responses." PLOS Pathogens 17, no. 2 (2021): e1009364. http://dx.doi.org/10.1371/journal.ppat.1009364.

Full text

Abstract:

Previously, we reported that cellular transcription factor ZASC1 facilitates DNA-dependent/RNA-independent recruitment of HIV-1 TAT and the cellular elongation factor P-TEFb to the HIV-1 promoter and is a critical factor in regulating HIV-1 transcriptional elongation (PLoS Path e1003712). Here we report that cellular transcription factor ZBTB2 is a novel repressor of HIV-1 gene expression. ZBTB2 strongly co-immunoprecipitated with ZASC1 and was dramatically relocalized by ZASC1 from the cytoplasm to the nucleus. Mutations abolishing ZASC1/ZBTB2 interaction prevented ZBTB2 nuclear relocalizatio

APA, Harvard, Vancouver, ISO, and other styles

31

Patel, Charvi A., Muhammad Mukhtar, and Roger J. Pomerantz. "Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis in Human Neuronal Cells." Journal of Virology 74, no. 20 (2000): 9717–26. http://dx.doi.org/10.1128/jvi.74.20.9717-9726.2000.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) causes AIDS dementia complex (ADC) in certain infected individuals. Recent studies have suggested that patients with ADC have an increased incidence of neuronal apoptosis leading to neuronal dropout. Of note, a higher level of the HIV-1 accessory protein Vpr has been detected in the cerebrospinal fluid of AIDS patients with neurological disorders. Moreover, extracellular Vpr has been shown to form ion channels, leading to cell death of cultured rat hippocampal neurons. Based on these previous fin

APA, Harvard, Vancouver, ISO, and other styles

32

Sherman, Michael P., Carlos M. C. de Noronha, Marina I. Heusch, Spencer Greene, and Warner C. Greene. "Nucleocytoplasmic Shuttling by Human Immunodeficiency Virus Type 1 Vpr." Journal of Virology 75, no. 3 (2001): 1522–32. http://dx.doi.org/10.1128/jvi.75.3.1522-1532.2001.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) is capable of infecting nondividing cells such as macrophages because the viral preintegration complex is able to actively traverse the limiting nuclear pore due to the redundant and possibly overlapping nuclear import signals present in Vpr, matrix, and integrase. We have previously recognized the presence of at least two distinct and novel nuclear import signals residing within Vpr that, unlike matrix and integrase, bypass the classical importin α/β-dependent signals and do not require energy or a RanGTP gradient. We now report that the ca

APA, Harvard, Vancouver, ISO, and other styles

33

Richard, Jonathan, Sardar Sindhu, Tram N. Q. Pham, Jean-Philippe Belzile, and Éric A. Cohen. "HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell–mediated killing." Blood 115, no. 7 (2010): 1354–63. http://dx.doi.org/10.1182/blood-2009-08-237370.

Full text

Abstract:

AbstractHIV up-regulates cell-surface expression of specific ligands for the activating NKG2D receptor, including ULBP-1, -2, and -3, but not MICA or MICB, in infected cells both in vitro and in vivo. However, the viral factor(s) involved in NKG2D ligand expression still remains undefined. HIV-1 Vpr activates the DNA damage/stress-sensing ATR kinase and promotes G2 cell-cycle arrest, conditions known to up-regulate NKG2D ligands. We report here that HIV-1 selectively induces cell-surface expression of ULBP-2 in primary CD4+ T lymphocytes by a process that is Vpr dependent. Importantly, Vpr enh

APA, Harvard, Vancouver, ISO, and other styles

34

Mansky, Louis M., Sandra Preveral, Luc Selig, Richard Benarous, and Serge Benichou. "The Interaction of Vpr with Uracil DNA Glycosylase Modulates the Human Immunodeficiency Virus Type 1 In Vivo Mutation Rate." Journal of Virology 74, no. 15 (2000): 7039–47. http://dx.doi.org/10.1128/jvi.74.15.7039-7047.2000.

Full text

Abstract:

ABSTRACT The Vpr protein of human immunodeficiency virus type 1 (HIV-1) influences the in vivo mutation rate of the virus. Since Vpr interacts with a cellular protein implicated in the DNA repair process, uracil DNA glycosylase (UNG), we have explored the contribution of this interaction to the mutation rate of HIV-1. Single-amino-acid variants of Vpr were characterized for their differential UNG-binding properties and used to trans complement vpr null mutant HIV-1. A striking correlation was established between the abilities of Vpr to interact with UNG and to influence the HIV-1 mutation rate

APA, Harvard, Vancouver, ISO, and other styles

35

Amini, Shohreh, Marcus Saunders, Kimberly Kelley, Kamel Khalili, and Bassel E. Sawaya. "Interplay between HIV-1 Vpr and Sp1 Modulates p21WAF1Gene Expression in Human Astrocytes." Journal of Biological Chemistry 279, no. 44 (2004): 46046–56. http://dx.doi.org/10.1074/jbc.m403792200.

Full text

Abstract:

The Vpr (viral protein R) of human immunodeficiency virus, type 1, which is expressed during the late stage of the viral infection, has received special attention because of its ability to control transcription of the human immunodeficiency virus, type 1, long terminal repeat and to influence cell cycle progression. Here we demonstrate that Vpr has the ability to regulate transcription of the cyclin-dependent kinase inhibitor, p21WAF1(p21), one of the key regulators of the cell cycle, in human astrocytic cells. The results from transcription assays demonstrated that Vpr augments promoter activ

APA, Harvard, Vancouver, ISO, and other styles

36

Votteler, Jörg, Nicole Studtrucker, Stefan Sörgel, et al. "Proline 35 of Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Regulates the Integrity of the N-Terminal Helix and the Incorporation of Vpr into Virus Particles and Supports the Replication of R5-Tropic HIV-1 in Human Lymphoid Tissue Ex Vivo." Journal of Virology 81, no. 17 (2007): 9572–76. http://dx.doi.org/10.1128/jvi.02803-06.

Full text

Abstract:

ABSTRACT Mutational analysis of the four conserved proline residues in human immunodeficiency virus type 1 (HIV-1) Vpr reveals that only Pro-35 is required for efficient replication of R5-tropic, but not of X4-tropic, viruses in human lymphoid tissue (HLT) cultivated ex vivo. While Vpr-mediated apoptosis and G2 cell cycle arrest, as well as the expression and subcellular localization of Vpr, were independent, the capacity for encapsidation of Vpr into budding virions was dependent on Pro-35. 1H nuclear magnetic resonance data suggest that mutation of Pro-35 causes a conformational change in th

APA, Harvard, Vancouver, ISO, and other styles

37

Mishra, Sasmita, Jyoti P. Mishra, and Ashok Kumar. "Activation of JNK-dependent Pathway Is Required for HIV Viral Protein R-induced Apoptosis in Human Monocytic Cells." Journal of Biological Chemistry 282, no. 7 (2006): 4288–300. http://dx.doi.org/10.1074/jbc.m608307200.

Full text

Abstract:

Human immunodeficiency virus (HIV) accessory protein viral protein R (Vpr) plays a key role in virus replication and induces cell cycle arrest and apoptosis in various cell types including T cells and neuronal and tumor cells following infection with Vpr-expressing HIV isolates or exposure to the extracellular Vpr protein. The C-terminal Vpr peptide encompassing amino acids 52–96 (Vpr-(52–96)) is required for exerting the apoptotic effects, whereas the N-terminal Vpr-(1–45) peptide is responsible for virus transcription. We demonstrate that Vpr-(52–96) induced apoptosis in human promonocytic T

APA, Harvard, Vancouver, ISO, and other styles

38

Chang, Hao, Lowela Siarot, Ryosuke Matsuura, et al. "Distinct MCM10 Proteasomal Degradation Profiles by Primate Lentiviruses Vpr Proteins." Viruses 12, no. 1 (2020): 98. http://dx.doi.org/10.3390/v12010098.

Full text

Abstract:

Viral protein R (Vpr) is an accessory protein found in various primate lentiviruses, including human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) as well as simian immunodeficiency viruses (SIVs). Vpr modulates many processes during viral lifecycle via interaction with several of cellular targets. Previous studies showed that HIV-1 Vpr strengthened degradation of Mini-chromosome Maintenance Protein10 (MCM10) by manipulating DCAF1-Cul4-E3 ligase in proteasome-dependent pathway. However, whether Vpr from other primate lentiviruses are also associated with MCM10 degradation and the ens

APA, Harvard, Vancouver, ISO, and other styles

39

Yuan, Huidong, Masakazu Kamata, Yi-Ming Xie, and Irvin S. Y. Chen. "Increased Levels of Wee-1 Kinase in G2 Are Necessary for Vpr- and Gamma Irradiation-Induced G2 Arrest." Journal of Virology 78, no. 15 (2004): 8183–90. http://dx.doi.org/10.1128/jvi.78.15.8183-8190.2004.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle arrest at the G2/M transition and subsequently apoptosis. Here we examined the potential involvement of Wee-1 in Vpr-induced G2 arrest. Wee-1 is a cellular protein kinase that inhibits Cdc2 activity, thereby preventing cells from proceeding through mitosis. We previously showed that the levels of Wee-1 correlate with Vpr-mediated apoptosis. Here, we demonstrate that Vpr-induced G2 arrest correlated with delayed degradation of Wee-1 at G2/M. Experimental depletion of Wee-1 by a small interfering RNA directed to wee-1 mR

APA, Harvard, Vancouver, ISO, and other styles

40

Yuan, Huidong, Yi-Ming Xie, and Irvin S. Y. Chen. "Depletion of Wee-1 Kinase Is Necessary for both Human Immunodeficiency Virus Type 1 Vpr- and Gamma Irradiation-Induced Apoptosis." Journal of Virology 77, no. 3 (2003): 2063–70. http://dx.doi.org/10.1128/jvi.77.3.2063-2070.2003.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus (HIV) protein R (Vpr) induces G2 arrest, and prolonged G2 arrest leads to apoptosis. We find that in HeLa cells the cell cycle regulatory kinase, Wee-1, is depleted following prolonged G2 arrest induced by Vpr. Of note, small interfering RNAs directed to Wee-1 triggered apoptosis, suggesting a direct role for Wee-1 in apoptosis. In support of this hypothesis, overexpression of Wee-1 suppressed Vpr-mediated apoptosis. Importantly, similar results were observed with cells induced to undergo apoptosis gamma irradiation. Thus, Wee-1 may serve as a key regulato

APA, Harvard, Vancouver, ISO, and other styles

41

Huard, Sylvain, Robert T. Elder, Dong Liang, Ge Li, and Richard Y. Zhao. "Human Immunodeficiency Virus Type 1 Vpr Induces Cell Cycle G2 Arrest through Srk1/MK2-Mediated Phosphorylation of Cdc25." Journal of Virology 82, no. 6 (2007): 2904–17. http://dx.doi.org/10.1128/jvi.01098-07.

Full text

Abstract:

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) and mammalian cells, suggesting the cellular pathway(s) targeted by Vpr is conserved among eukaryotes. Our previous studies in fission yeast demonstrated that Vpr induces G2 arrest in part through inhibition of Cdc25, a Cdc2-specific phosphatase that promotes G2/M transition. The goal of this study was to further elucidate molecular mechanism underlying the inhibitory effect of Vpr on Cdc25. We show here that, similar to the DNA checkpoint controls, expression of v

APA, Harvard, Vancouver, ISO, and other styles

42

Fritz, Joëlle V., Denis Dujardin, Julien Godet, et al. "HIV-1 Vpr Oligomerization but Not That of Gag Directs the Interaction between Vpr and Gag." Journal of Virology 84, no. 3 (2009): 1585–96. http://dx.doi.org/10.1128/jvi.01691-09.

Full text

Abstract:

ABSTRACT During HIV-1 assembly, the viral protein R (Vpr) is incorporated into newly made viral particles via an interaction with the C-terminal domain of the Gag polyprotein precursor Pr55Gag. Vpr has been implicated in the nuclear import of newly made viral DNA and subsequently in its transcription. In addition, Vpr can affect the cell physiology by causing G2/M cell cycle arrest and apoptosis. Vpr can form oligomers, but their roles have not yet been investigated. We have developed fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer-based assays to monitor the in

APA, Harvard, Vancouver, ISO, and other styles

43

Selig, L., J. C. Pages, V. Tanchou, et al. "Interaction with the p6 Domain of the Gag Precursor Mediates Incorporation into Virions of Vpr and Vpx Proteins from Primate Lentiviruses." Journal of Virology 73, no. 1 (1999): 592–600. http://dx.doi.org/10.1128/jvi.73.1.592-600.1999.

Full text

Abstract:

ABSTRACT Vpr and Vpx proteins from human and simian immunodeficiency viruses (HIV and SIV) are incorporated into virions in quantities equivalent to those of the viral Gag proteins. We demonstrate here that Vpr and Vpx proteins from distinct lineages of primate lentiviruses were able to bind to their respective Gag precursors. The capacity of HIV type 1 (HIV-1) Vpr mutants to bind to Pr55Gag was correlated with their incorporation into virions. Molecular analysis of these interactions revealed that they required the C-terminal p6 domain of the Gag precursors. While the signal for HIV-1 Vpr bin

APA, Harvard, Vancouver, ISO, and other styles

44

Yan, Qin, Chenyou Shen, Jie Qin та ін. "HIV-1 Vpr Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication by Inducing MicroRNA miR-942-5p and Activating NF-κB Signaling". Journal of Virology 90, № 19 (2016): 8739–53. http://dx.doi.org/10.1128/jvi.00797-16.

Full text

Abstract:

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) infection is required for the development of several AIDS-related malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). The high incidence of AIDS-KS has been ascribed to the interaction of KSHV and HIV-1. We have previously shown that HIV-1-secreted proteins Tat and Nef regulate the KSHV life cycle and synergize with KSHV oncogenes to promote angiogenesis and tumorigenesis. Here, we examined the regulation of KSHV latency by HIV-1 viral protein R (Vpr). We found that soluble Vpr inhibits the expression of KSHV

APA, Harvard, Vancouver, ISO, and other styles

45

Jenkins, Yonchu, Patricia V. Sanchez, Barbara E. Meyer, and Michael H. Malim. "Nuclear Export of Human Immunodeficiency Virus Type 1 Vpr Is Not Required for Virion Packaging." Journal of Virology 75, no. 17 (2001): 8348–52. http://dx.doi.org/10.1128/jvi.75.17.8348-8352.2001.

Full text

Abstract:

ABSTRACT The human immunodeficiency virus type 1 Vpr protein is both packaged into virions and efficiently localized to the nucleus. In this report, we show that a significant fraction of Vpr also accumulates in the cytoplasm of virus-producing cells. Although Vpr shuttles between the nucleus and the cytoplasm, studies with an export-deficient Vpr mutant reveal that nuclear export is not required for virion incorporation.

APA, Harvard, Vancouver, ISO, and other styles

46

Shimura, Mari, Yusuke Toyoda, Kenta Iijima, et al. "Epigenetic displacement of HP1 from heterochromatin by HIV-1 Vpr causes premature sister chromatid separation." Journal of Cell Biology 194, no. 5 (2011): 721–35. http://dx.doi.org/10.1083/jcb.201010118.

Full text

Abstract:

Although pericentromeric heterochromatin is essential for chromosome segregation, its role in humans remains controversial. Dissecting the function of HIV-1–encoded Vpr, we unraveled important properties of heterochromatin during chromosome segregation. In Vpr-expressing cells, hRad21, hSgo1, and hMis12, which are crucial for proper chromosome segregation, were displaced from the centromeres of mitotic chromosomes, resulting in premature chromatid separation (PCS). Interestingly, Vpr displaced heterochromatin protein 1-α (HP1-α) and HP1-γ from chromatin. RNA interference (RNAi) experiments rev

APA, Harvard, Vancouver, ISO, and other styles

47

Zhu, Yonghong, Harris A. Gelbard, Mikhail Roshal, Shannon Pursell, Beth D. Jamieson, and Vicente Planelles. "Comparison of Cell Cycle Arrest, Transactivation, and Apoptosis Induced by the Simian Immunodeficiency Virus SIVagm and Human Immunodeficiency Virus Type 1 vpr Genes." Journal of Virology 75, no. 8 (2001): 3791–801. http://dx.doi.org/10.1128/jvi.75.8.3791-3801.2001.

Full text

Abstract:

ABSTRACT All primate lentiviruses known to date contain one or two open reading frames with homology to the human immunodeficiency virus type 1 (HIV-1) vpr gene. HIV-1 vpr encodes a 96-amino-acid protein with multiple functions in the viral life cycle. These functions include modulation of the viral replication kinetics, transactivation of the long terminal repeat, participation in the nuclear import of preintegration complexes, induction of G2arrest, and induction of apoptosis. The simian immunodeficiency virus (SIV) that infects African green monkeys (SIVagm) contains avpr homologue, which e

APA, Harvard, Vancouver, ISO, and other styles

48

Barnitz, R. Anthony, Fengyi Wan, Vinay Tripuraneni, Diane L. Bolton, and Michael J. Lenardo. "Protein Kinase A Phosphorylation Activates Vpr-Induced Cell Cycle Arrest during Human Immunodeficiency Virus Type 1 Infection." Journal of Virology 84, no. 13 (2010): 6410–24. http://dx.doi.org/10.1128/jvi.02273-09.

Full text

Abstract:

ABSTRACT Infection with human immunodeficiency virus type 1 (HIV-1) causes an inexorable depletion of CD4+ T cells. The loss of these cells is particularly pronounced in the mucosal immune system during acute infection, and the data suggest that direct viral cytopathicity is a major factor. Cell cycle arrest caused by the HIV-1 accessory protein Vpr is strongly correlated with virus-induced cell death, and phosphorylation of Vpr serine 79 (S79) is required to activate G2/M cell cycle blockade. However, the kinase responsible for phosphorylating Vpr remains unknown. Our bioinformatic analyses r

APA, Harvard, Vancouver, ISO, and other styles

49

Kino, Tomoshige, Alexander Gragerov, Jeffrey B. Kopp, Roland H. Stauber, George N. Pavlakis, and George P. Chrousos. "The HIV-1 Virion-associated Protein Vpr Is a Coactivator of the Human Glucocorticoid Receptor." Journal of Experimental Medicine 189, no. 1 (1999): 51–62. http://dx.doi.org/10.1084/jem.189.1.51.

Full text

Abstract:

The HIV-1 virion-associated accessory protein Vpr affects both viral replication and cellular transcription, proliferation, and differentiation. We report that Vpr enhances the activity of glucocorticoids in lymphoid and muscle-derived cell lines by interacting directly with the glucocorticoid receptor and general transcription factors, acting as a coactivator. Vpr contains the signature motif LXXLL also present in cellular nuclear receptor coactivators, such as steroid receptor coactivator 1 and p300/CREB-binding protein, which mediates their interaction with the glucocorticoid and other nucl

APA, Harvard, Vancouver, ISO, and other styles

50

Müller, Barbara, Uwe Tessmer, Ulrich Schubert, and Hans-Georg Kräusslich. "Human Immunodeficiency Virus Type 1 Vpr Protein Is Incorporated into the Virion in Significantly Smaller Amounts than Gag and Is Phosphorylated in Infected Cells." Journal of Virology 74, no. 20 (2000): 9727–31. http://dx.doi.org/10.1128/jvi.74.20.9727-9731.2000.

Full text

Abstract:

ABSTRACT Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is a small accessory protein involved in the nuclear import of viral DNA and the growth arrest of host cells. Several studies have demonstrated that a significant amount of Vpr is incorporated into the virus particle via interaction with the p6 domain of Gag, and it is generally assumed that Vpr is packaged in equimolar ratio to Gag. We have quantitated the relative amount of Vpr in purified virions following [35S]cysteine labeling of infected MT-4 cells, as well as by quantitative immunoblotting and found that Vpr i

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!