Functional changes in astrocytes by human T-lymphotropic virus type-1 T-lymphocytes

Akaoka, H.; Szymocha, Raphaël; Beurton-Marduel, Patricia; Bernard, Arlette; Belin, Marie‐Françoise; Giraudon, Pascale

doi:10.1016/s0168-1702(01)00284-2

Cited by 17 publications

(10 citation statements)

References 31 publications

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“…Although in vivo results have not shown conclusively that astrocytes are infected in HTLV-Ipositive individuals, experimental results utilizing primary astrocytes infected with HTLV-I in vitro have suggested that astrocytes may be infected in vivo and that viral infection of this cell type may play a role in the pathogenesis of HAM/TSP (25,26,34,35). In previous studies, HTLV-I-infected astrocytes exhibited Tax accumulation in the nucleus and also to a significant extent in the cytoplasm (26).…”

Section: Tax-yfp/gfp Intracellular Distribution Ismentioning

confidence: 96%

Characterization of a Nuclear Export Signal within the Human T Cell Leukemia Virus Type I Transactivator Protein Tax

Alefantis

Barmak

Harhaj

et al. 2003

Journal of Biological Chemistry

107

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Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-Iassociated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response elementbinding protein and nuclear factor-B, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucinerich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant Tax⌬214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

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Section: Tax-yfp/gfp Intracellular Distribution Ismentioning

confidence: 96%

Characterization of a Nuclear Export Signal within the Human T Cell Leukemia Virus Type I Transactivator Protein Tax

Alefantis

Barmak

Harhaj

et al. 2003

Journal of Biological Chemistry

107

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“…These pathways, however, are probably of minor significance as compared to the prominent lactate production. Lactate release by astrocytes was found to be stimulated upon exposure to glutamate (Pellerin and Magistretti 1994; Akaoka et al . 2001).…”

Section: Importance Of Monocarboxylate Utilization By the Brainmentioning

confidence: 99%

Monocarboxylate transporters in the central nervous system: distribution, regulation and function

Pierre¹,

Pellerin²

2005

Journal of Neurochemistry

588

469

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Monocarboxylate transporters (MCTs) are proton-linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as ketone bodies. They belong to a larger family of transporters composed of 14 members in mammals based on sequence homologies. MCTs are found in various tissues including the brain where three isoforms, MCT1, MCT2 and MCT4, have been described. Each of these isoforms exhibits a distinct regional and cellular distribution in rodent brain. At the cellular level, MCT1 is expressed by endothelial cells of microvessels, by ependymocytes as well as by astrocytes. MCT4 expression appears to be specific for astrocytes. By contrast, the predominant neuronal monocarboxylate transporter is MCT2. Interestingly, part of MCT2 immunoreactivity is located at postsynaptic sites, suggesting a particular role of monocarboxylates and their transporters in synaptic transmission. In addition to variation in expression during development and upon nutritional modifications, new data indicate that MCT expression is regulated at the translational level by neurotransmitters. Understanding how transport of monocarboxylates is regulated could be of particular importance not only for neuroenergetics but also for areas such as functional brain imaging, regulation of food intake and glucose homeostasis, or for central nervous system disorders such as ischaemia and neurodegenerative diseases.

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“…A general effect of HTLV-1 infection is to reduce lactate production and glucose consumption, and cells starved of glucose are more readily infected by HTLV-1 as well. However, in certain cell types, HTLV-1 infection results in enhanced glucose uptake and lactate production, which indicate that the metabolic disturbances induced by HTLV-1 are cell type-specific (40). These effects may result from enhanced GLUT1 expression in certain cells, which would be beneficial for HTLV-1 infection.…”

Section: Transforming Viruses Trigger Alterations In Glucose Uptake Bmentioning

confidence: 99%

Oncogenic Viruses and Tumor Glucose Metabolism: Like Kids in a Candy Store

Noch

Khalili

2012

Molecular Cancer Therapeutics

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Oncogenic viruses represent a significant public health burden in light of the multitude of malignancies resulting from chronic or spontaneous viral infection and transformation. Though many of the molecular signaling pathways underlying virus-mediated cellular transformation are known, the impact of these viruses on metabolic signaling and phenotype within proliferating tumor cells is less well understood. Whether the interaction of oncogenic viruses with metabolic signaling pathways involves enhanced glucose uptake and glycolysis, both hallmark features of transformed cells, or dysregulation of molecular pathways regulating oxidative stress, viruses are adept at facilitating tumor expansion. Through their effects on cell proliferation pathways, such as the PI3K and MAPK pathways, the cell cycle regulatory proteins, p53 and ATM, and the cell stress response proteins, HIF-1α and AMPK, viruses exert control over critical metabolic signaling cascades. Additionally, oncogenic viruses modulate the tumor metabolomic profile through direct and indirect interaction with glucose transporters, such as GLUT1, and specific glycolytic enzymes, including pyruvate kinase, glucose 6-phosphate dehydrogenase, and hexokinase. Through these pathways, oncogenic viruses alter the phenotypic characteristics of transformed cells and their methods of energy utilization, and it may be possible to develop novel anti-glycolytic therapies to target these dysregulated pathways in virus-derived malignancies.

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Functional changes in astrocytes by human T-lymphotropic virus type-1 T-lymphocytes

Cited by 17 publications

References 31 publications

Characterization of a Nuclear Export Signal within the Human T Cell Leukemia Virus Type I Transactivator Protein Tax

Characterization of a Nuclear Export Signal within the Human T Cell Leukemia Virus Type I Transactivator Protein Tax

Monocarboxylate transporters in the central nervous system: distribution, regulation and function

Oncogenic Viruses and Tumor Glucose Metabolism: Like Kids in a Candy Store

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