Reference : Glucose Metabolism and Oxygen Availability Govern Reactivation of the Latent Human Re...
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Chemistry
Glucose Metabolism and Oxygen Availability Govern Reactivation of the Latent Human Retrovirus HTLV-1.
Kulkarni, Anurag [> >]
Mateus, Manuel [> >]
Thinnes, Cyrille mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
McCullagh, James S. [> >]
Schofield, Christopher J. [> >]
Taylor, Graham P. [> >]
Bangham, Charles R. M. [> >]
Cell chemical biology
Yes (verified by ORBilu)
United States
[en] Amino Acids, Dicarboxylic/pharmacology ; Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism ; CD4-Positive T-Lymphocytes/cytology/metabolism/virology ; Cell Hypoxia ; Cells, Cultured ; Citric Acid Cycle/drug effects ; Electron Transport Chain Complex Proteins/metabolism ; Epigenesis, Genetic ; Glucose/metabolism ; Glycolysis/drug effects ; Histones/genetics/metabolism ; Human T-lymphotropic virus 1/genetics/physiology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Ketoglutaric Acids/pharmacology ; Leukocytes, Mononuclear/cytology/metabolism/virology ; Mitochondria/drug effects/metabolism ; Oxygen/metabolism ; Virus Latency ; Virus Replication/drug effects ; 2-oxoglutarate ; HIF hydroxylase ; HTLV-1 ; epigenetic regulation ; glucose ; hypoxia ; latency ; metabolism ; virus
[en] The human retrovirus HTLV-1 causes a hematological malignancy or neuroinflammatory disease in approximately 10% of infected individuals. HTLV-1 primarily infects CD4(+) T lymphocytes and persists as a provirus integrated in their genome. HTLV-1 appears transcriptionally latent in freshly isolated cells; however, the chronically active anti-HTLV-1 cytotoxic T cell response observed in infected individuals indicates frequent proviral expression in vivo. The kinetics and regulation of HTLV-1 proviral expression in vivo are poorly understood. By using hypoxia, small-molecule hypoxia mimics, and inhibitors of specific metabolic pathways, we show that physiologically relevant levels of hypoxia, as routinely encountered by circulating T cells in the lymphoid organs and bone marrow, significantly enhance HTLV-1 reactivation from latency. Furthermore, culturing naturally infected CD4(+) T cells in glucose-free medium or chemical inhibition of glycolysis or the mitochondrial electron transport chain strongly suppresses HTLV-1 plus-strand transcription. We conclude that glucose metabolism and oxygen tension regulate HTLV-1 proviral latency and reactivation in vivo.
Copyright (c) 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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