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

in Cell chemical biology (2017), 24(11), 1377-13873

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 ... [more ▼]

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. [less ▲]