Akaoka H, Szymocha R, Beurton-Marduel P, Bernard A, Belin M F, Giraudon P
Faculte de Medecine Laennec, Experimental Neurobiology and Physiopathology, INSERM U433, F69372 Cedex 08, Lyon, France.
Virus Res. 2001 Oct 30;78(1-2):57-66. doi: 10.1016/s0168-1702(01)00284-2.
The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of a chronic progressive myelopathy (TSP/HAM) in which lesions of the central nervous system (CNS) are associated with infiltration of HTLV-1-infected T-cells. In a model that mimics the interaction between glial and T-cells, we show that transient contact with T-lymphocytes chronically infected with HTLV-1 induce profound metabolic alterations in astrocytes. Within the first week post-contact, an overall activation of astrocyte metabolism was observed as assessed by enhanced uptake of glutamate and glucose, and lactate release. In contrast, longer examination showed a reduced astrocytic accumulation of glutamate. The time course of the change in glutamate uptake was in fact biphasic. Previous observations indicated that HTLV-1 protein Tax-1 was involved in this delayed decrease, via the induction of TNF-alpha. The expression of the glial glutamate transporters, GLAST and GLT-1 decreased in parallel. These decreases in glutamate uptake and transporters' expression were associated with an imbalance in the expression of the catabolic enzymes of glutamate, GS and GDH, presumably due to Tax-1. Given the fact that impairment of glutamate management in astrocytes is able to compromise the functional integrity of neurons and oligodendrocytes, our results altogether give new insights into the physiopathology of TSP/HAM.
人类嗜T淋巴细胞病毒1型（HTLV-1）是一种慢性进行性脊髓病（TSP/HAM）的病原体，其中中枢神经系统（CNS）的病变与HTLV-1感染的T细胞浸润有关。在一个模拟神经胶质细胞与T细胞相互作用的模型中，我们发现与长期感染HTLV-1的T淋巴细胞短暂接触会诱导星形胶质细胞发生深刻的代谢改变。在接触后的第一周内，通过增强谷氨酸和葡萄糖摄取以及乳酸释放评估，观察到星形胶质细胞代谢全面激活。相反，更长时间的观察显示星形胶质细胞内谷氨酸积累减少。谷氨酸摄取变化的时间进程实际上是双相的。先前的观察表明，HTLV-1蛋白Tax-1通过诱导肿瘤坏死因子-α参与了这种延迟性减少。神经胶质谷氨酸转运体GLAST和GLT-1的表达也随之平行下降。谷氨酸摄取和转运体表达的这些下降与谷氨酸分解代谢酶GS和GDH表达失衡有关，推测是由Tax-1引起的。鉴于星形胶质细胞中谷氨酸管理受损会损害神经元和少突胶质细胞的功能完整性，我们的研究结果为TSP/HAM的病理生理学提供了新的见解。
