Schavinsky-Khrapunsky Yana, Gold Evgenia, Ben-Aroya Zahi, Torgeman Amram, Aboud Mordechai, Huleihel Mahmoud
Department of Microbiology and Immunology, Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Int J Mol Med. 2003 Jan;11(1):3-11.
HTLV-I is the etiological agent of adult T-cell leukemia (ATL), tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) and certain other clinical disorders. After infection in human the virus enters into a latent state, in which very low viral gene expression can be detected. On the other hand several major characteristics of ATL and TSP/HAM indicate that their genesis requires activation of the dormant virus. TSP/HAM is characterized by high virus expression, which accounts for most of its immunopathological manifestations, whereas the process leading to ATL is believed to be initiated by the viral Tax protein, implying that it requires, at least, a temporary activation of the latent virus. Data from our and other laboratories suggest that this activation may likely be induced by environmental or/and intrinsic apoptosis-inducing factors. Moreover, we have demonstrated a mechanistic linkage between the activation of the viral promoter and the early stage of the apoptotic cascade. However, we have also shown that Tax rescues virus-expressing T-cells from apoptotic death. This suggests that Tax protein, emerging after activation of the latent virus, can rescue the host cells of the activated virus from the ultimate apoptotic death. Since the development of both TSP/HAM and ATL seems to depend on the viral Tax protein, we describe a possible system for anti Tax gene-therapy approach based on a negative transdominant mutant Tax gene.
人类嗜T淋巴细胞病毒I型（HTLV-I）是成人T细胞白血病（ATL）、热带痉挛性截瘫/HTLV-I相关脊髓病（TSP/HAM）及某些其他临床疾病的病原体。病毒感染人体后进入潜伏状态，在此状态下只能检测到极低水平的病毒基因表达。另一方面，ATL和TSP/HAM的几个主要特征表明，它们的发生需要激活潜伏病毒。TSP/HAM的特点是病毒高表达，这构成了其大部分免疫病理表现，而导致ATL的过程据信是由病毒Tax蛋白启动的，这意味着它至少需要潜伏病毒的暂时激活。我们实验室和其他实验室的数据表明，这种激活可能是由环境或/和内在的凋亡诱导因子诱导的。此外，我们已经证明了病毒启动子的激活与凋亡级联反应早期之间的机制联系。然而，我们也表明Tax能使表达病毒的T细胞免于凋亡死亡。这表明潜伏病毒激活后出现的Tax蛋白可以使被激活病毒的宿主细胞免于最终的凋亡死亡。由于TSP/HAM和ATL的发展似乎都依赖于病毒Tax蛋白，我们描述了一种基于负性反式显性突变Tax基因的抗Tax基因治疗方法的可能系统。
