Cancer Institute, Medical Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Viruses. 2011 Jun;3(6):714-49. doi: 10.3390/v3060714.
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATL), whereas the highly related HTLV-2 is not associated with ATL or other cancers. In addition to ATL leukemogenesis, studies of the HTLV viruses also provide an exceptional model for understanding basic pathogenic mechanisms of virus-host interactions and human oncogenesis. Accumulating evidence suggests that the viral regulatory protein Tax and host inflammatory transcription factor NF-κB are largely responsible for the different pathogenic potentials of HTLV-1 and HTLV-2. Here, we discuss the molecular mechanisms of HTLV-1 oncogenic pathogenesis with a focus on the interplay between the Tax oncoprotein and NF-κB pro-oncogenic signaling. We also outline some of the most intriguing and outstanding questions in the fields of HTLV and NF-κB. Answers to those questions will greatly advance our understanding of ATL leukemogenesis and other NF-κB-associated tumorigenesis and will help us design personalized cancer therapies.
人类 T 细胞白血病病毒 1 型（HTLV-1）是成人 T 细胞白血病/淋巴瘤（ATL）的病原体，而高度相关的 HTLV-2 则与 ATL 或其他癌症无关。除了 ATL 白血病的发生外，对 HTLV 病毒的研究还为理解病毒-宿主相互作用和人类致癌的基本发病机制提供了一个特殊的模型。越来越多的证据表明，病毒调节蛋白 Tax 和宿主炎症转录因子 NF-κB 在很大程度上负责 HTLV-1 和 HTLV-2 的不同致病潜力。在这里，我们讨论了 HTLV-1 致癌发病机制的分子机制，重点是 Tax 癌蛋白和 NF-κB 致癌信号之间的相互作用。我们还概述了 HTLV 和 NF-κB 领域中一些最有趣和最突出的问题。这些问题的答案将极大地促进我们对 ATL 白血病发生和其他 NF-κB 相关肿瘤发生的理解，并帮助我们设计个性化的癌症治疗方法。
