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Cell Chem Biol. 2017 Nov 16;24(11):1377-1387.e3. doi: 10.1016/j.chembiol.2017.08.016. Epub 2017 Sep 28.

Glucose Metabolism and Oxygen Availability Govern Reactivation of the Latent Human Retrovirus HTLV-1.

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Section of Virology, Department of Medicine, Imperial College, London W2 1PG, UK.
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, UK.
Section of Virology, Department of Medicine, Imperial College, London W2 1PG, UK. Electronic address:


The human retrovirus HTLV-1 causes a hematological malignancy or neuroinflammatory disease in ∼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.


2-oxoglutarate; HIF hydroxylase; HTLV-1; epigenetic regulation; glucose; hypoxia; latency; metabolism; virus

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