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 expressionin vivo. The kinetics and regulation of HTLV-1 proviral expressionin vivoare 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 reactivationin vivo.

中文翻译：

---

葡萄糖代谢和氧供应控制潜在的人类逆转录病毒HTLV-1的激活。

人类逆转录病毒HTLV-1在约10％的感染个体中引起血液系统恶性肿瘤或神经炎性疾病。HTLV-1主要感染CD4 + T淋巴细胞，并以整合在其基因组中的原病毒形式持续存在。HTLV-1在新鲜分离的细胞中似乎具有转录潜伏性。但是，在受感染的个体中观察到的具有慢性活性的抗HTLV-1细胞毒性T细胞反应表明，体内存在频繁的前病毒表达。体内对HTLV-1前病毒表达的动力学和调控了解甚少。通过使用缺氧，小分子缺氧模拟物和特定代谢途径的抑制剂，我们显示了生理相关水平的缺氧，如淋巴器官和骨髓中循环T细胞通常遇到的，显着增强了潜伏期HTLV-1的重新激活。此外，在无葡萄糖的培养基中培养天然感染的CD4 + T细胞，或者对糖酵解或线粒体电子传输链进行化学抑制，都会强烈抑制HTLV-1正链转录。我们得出结论，葡萄糖代谢和氧张力调节体内HTLV-1前病毒潜伏期和再激活。