![]() HTLV-1 infection is considered to be largely latent in infected individuals, because the viral structural RNA and protein products are usually undetectable in freshly isolated infected peripheral blood mononuclear cells (PBMCs) ( Hanon et al., 2000, Rende et al., 2011). In a subset of infected individuals (∼5%–10%), however, HTLV-1 infection progresses to either a CD4 + T cell malignancy known as adult T cell leukemia/lymphoma or to HTLV-1-associated myelopathy, a progressive inflammatory disease of the spinal cord. HTLV-1 infection is asymptomatic in most cases. ![]() It is estimated that 5–10 million people worldwide are HTLV-1 carriers. It is a single-stranded positive-sense RNA virus that reverse transcribes its RNA genome and integrates the resulting double-stranded DNA copy of its genome into the host cellular chromatin (as a provirus), thereby establishing a persistent infection in the cells. HTLV-1 is a human retrovirus that primarily infects CD4 + T lymphocytes. ![]() We conclude that glucose metabolism and oxygen tension regulate HTLV-1 proviral latency and reactivation in vivo. ![]() 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. 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. The kinetics and regulation of HTLV-1 proviral expression in vivo are poorly understood. ![]() 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. HTLV-1 primarily infects CD4 + T lymphocytes and persists as a provirus integrated in their genome. The human retrovirus HTLV-1 causes a hematological malignancy or neuroinflammatory disease in ∼10% of infected individuals. ![]()
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