HIV-1 Vpr: Mechanisms of G2 arrest and apoptosis

Andersen, Joshua L.; Rouzic, Erwann Le; Planelles, Vicente

doi:10.1016/j.yexmp.2008.03.015

Cited by 97 publications

(93 citation statements)

References 146 publications

(174 reference statements)

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“…From this aspect, our data are in line with the earlier immunoblot findings that the vpr expression starts at 15-17 h, leading to morphological changes in the 17-h cultures [19]. The G2/M cell cycle block may be detected in the 35-h cultures, leading to apoptosis preceded by morphological changes [1,30]. Chang et al [6] found that wild-type vpr-expressing S. pombe cells began to exhibit elongation at 19 h and were lengthened progressively at 24 h. Morphological changes were observed at 20 h in mutant F34Ivpr-expressing S. pombe cultures, in which 20% of the cells were in the mitotic phase, with more than half displaying elongated morphology [28].…”

Section: Nl4-3vpr Expression-induced Growth Inhibition Cell Cycle G2supporting

confidence: 92%

Regulation of unbalanced redox homeostasis induced by the expression of wild-type HIV-1 viral protein R (NL4-3Vpr) in fission yeast

Gazdag

Stromájer-Rácz

Belágyi

et al. 2015

Acta Biologica Hungarica

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The wild-type viral protein R (Vpr) of human immunodeficiency virus type 1 exerts multiple effects on cellular activities during infection, including the induction of cell cycle G 2 arrest and the death of human cells and cells of the fission yeast Schizosaccharomyces pombe. In this study, wild-type Vpr (NL4-3Vpr) integrated as a single copy gene in S. pombe chromosome was used to investigate the molecular impact of Vpr on cellular oxidative stress. NL4-3Vpr triggered an atypical response in early (14-h), and a wellregulated oxidative stress response in late (35-h) log-phase cultures. Specifically, NL4-3Vpr expression induced oxidative stress in the 14-h cultures leading, to decreased levels of superoxide anion (O 2 • -), hydroxyl radical ( • OH) and glutathione (GSH), and significantly decreased activities of catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione S-transferase. In the 35-h cultures, elevated levels of O 2 • -and peroxides were accompanied by increased activities of most antioxidant enzymes, suggesting that the Vpr-induced unbalanced redox state of the cells might contribute to the adverse effects in HIV-infected patients.

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Section: Nl4-3vpr Expression-induced Growth Inhibition Cell Cycle G2supporting

confidence: 92%

Regulation of unbalanced redox homeostasis induced by the expression of wild-type HIV-1 viral protein R (NL4-3Vpr) in fission yeast

Gazdag

Stromájer-Rácz

Belágyi

et al. 2015

Acta Biologica Hungarica

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“…However, neither HIV-2 nor simian immunodeficiency virus Vpr induces apoptosis in mammalian cell lines. Induction of apoptosis by several HIV-1 proteins, including Nef, Vif, Vpr, Vpu, Tat and Rev, has also been reported (Andersen et al, 2008;Chang et al, 2000;Conti et al, 2000;Stewart et al, 1999;Yedavalli et al, 2005).…”

Section: Induction Of Apoptosismentioning

confidence: 92%

Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

Romani

Engelbrecht

2009

Journal of General Virology

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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, understanding the functions of Vpr usually involves the study of cellular pathways. Several functions of Vpr are attributed to the virion-incorporated protein, but some of them are attributed to the expression of Vpr in HIV-1-infected cells. The structure of Vpr may be key to understanding the variety of its interactions. Due to the critical role of Vpr in HIV-1 pathogenicity, study of the interactions between Vpr and cellular proteins may help us to understand the mechanism(s) of HIV-1 pathogenicity.

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“…10 Vpr is known to induce cell cycle arrest in G 2 /M phase. 11,12 Vpr-mediated pathogenesis in macrophages has been extensively investigated, [13][14][15] but its effects on the global molecular mechanism associated with metabolic pathways have not been characterized. Our recent SILAC-based proteomics study showed that HIV-1 Vpr overexpression in macrophages induces changes at the protein level in many of the enzymes involved in cellular metabolism.…”

Section: Introductionmentioning

confidence: 99%

Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr

et al. 2016

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HIV-1 infected macrophages play a significant role in the neuropathogenesis of AIDS. HIV-1 viral protein R (Vpr) not only facilitates HIV-1 infection but also contribute to long-lived persistence in macrophages. Our previous studies using SILAC-based proteomic analysis showed that the expression of critical metabolic enzymes in the glycolytic pathway and tricarboxylic acid (TCA) cycle were altered in response to Vpr expression in macrophages. We hypothesized that Vpr-induced modulation of glycolysis and TCA cycle regulates glutamate metabolism and release in HIV-1 infected macrophages.We assessed the amount of specific metabolites induced by Vpr and HIV-1 in macrophages at the intracellular and extracellular level in a time-dependent manner utilizing multiple reaction monitoring (MRM) targeted metabolomics. In addition, stable isotope-labeled glucose and an MRM targeted metabolomics assay were used to evaluate the de novo synthesis and release of glutamate in Vpr overexpressing macrophages and HIV-1 infected macrophages, throughout the metabolic flux of glycolytic pathway and TCA cycle activation.The metabolic flux studies demonstrated an increase in glucose uptake, glutamate release and accumulation of a-ketoglutarate (a-KG) and glutamine in the extracellular milieu in Vpr expressing and HIV-1 infected macrophages. Interestingly, glutamate pools and other intracellular intermediates (glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), citrate, malate, a-KG, and glutamine) showed a decreased trend except for fumarate, in contrast to the glutamine accumulation observed in the extracellular space in Vpr overexpressing macrophages.Our studies demonstrate that dysregulation of mitochondrial glutamate metabolism induced by Vpr in HIV-1 infected macrophages commonly seen, may contribute to neurodegeneration via excitotoxic mechanisms in the context of NeuroAIDS.

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HIV-1 Vpr: Mechanisms of G2 arrest and apoptosis

Cited by 97 publications

References 146 publications

Regulation of unbalanced redox homeostasis induced by the expression of wild-type HIV-1 viral protein R (NL4-3Vpr) in fission yeast

Regulation of unbalanced redox homeostasis induced by the expression of wild-type HIV-1 viral protein R (NL4-3Vpr) in fission yeast

Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr

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