Marino-Merlo Francesca, Grelli Sandro, Mastino Antonio, Lai Michele, Ferrari Paola, Nicolini Andrea, Pistello Mauro, Macchi Beatrice
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
Department of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Int J Mol Sci. 2023 Sep 30;24(19):14807. doi: 10.3390/ijms241914807.
The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a type of cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through the body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5-10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM/TSP). ATL is characterized by a low viral expression and poor prognosis. The oncogenic mechanism triggered by HTLV-1 is extremely complex and the molecular pathways are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed Tcell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt regulated cell death, thereby exerting their transforming effects. This review provides updated information on the mechanisms underlying the transforming action of HTLV-1 and highlights potential therapeutic targets to combat ATL.
人类嗜T淋巴细胞病毒1型（HTLV-1）是已知的唯一一种人类致癌逆转录病毒。HTLV-1可引发一种名为成人T细胞白血病/淋巴瘤（ATL）的癌症。该病毒通过受感染个体的体液传播，主要是母乳、血液和精液。世界上至少有500万至1000万人感染了HTLV-1。除了ATL，HTLV-1感染还可导致HTLV-I相关脊髓病（HAM/TSP）。ATL的特点是病毒表达水平低且预后不良。HTLV-1引发的致癌机制极其复杂，分子途径尚未完全明确。然而，病毒调节蛋白Tax和HTLV-1碱性亮氨酸拉链因子（HBZ）已被证明在HTLV-1感染的T细胞转化中起关键作用。此外，多项研究表明，HTLV-1感染的转化T细胞克隆的最终命运是HTLV-1致癌蛋白表达与细胞转录因子复杂相互作用的结果，这些转录因子会破坏细胞周期并干扰程序性细胞死亡，从而发挥其转化作用。本综述提供了关于HTLV-1转化作用机制的最新信息，并强调了对抗ATL的潜在治疗靶点。
