Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles
Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles
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DOI：
10.1182/blood-2010-06-293340
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发表时间：
2011-08-11
期刊：
影响因子：
20.3
通讯作者：
Franchini, Genoveffa
中科院分区：
文献类型：
--
作者：
Andresen, Vibeke;Pise-Masison, Cynthia A.;Franchini, Genoveffa
人类T细胞白血病病毒1型(HTLV-1)感染者的疾病发展与T细胞内整合病毒DNA水平呈正相关。HTLV-1复制受Tax和Rex正调控，受P30和HBZ蛋白负调控。在本研究中，我们证明HTLV-1编码另一种病毒表达的负调控蛋白p13蛋白。单独表达时，p13定位于线粒体，而在Tax存在的情况下，部分p13被泛素化、稳定并重新路由到核斑点。P13蛋白直接与Tax结合，减少Tax与CBP/p300转录辅活化子的结合，并通过降低Tax转录活性抑制病毒表达。因为Tax稳定了它自己的抑制子，这些发现表明HTLV-1已经进化出一种复杂的机制来控制自己的复制。此外，这些结果强调了研究HTLV-1病毒蛋白功能的重要性，不仅在分离中，而且在病毒完全复制的背景下也是如此。(血。2011年；118(6)：1549-1559)
Disease development in human T-cell leukemia virus type 1 (HTLV-1)-infected individuals is positively correlated with the level of integrated viral DNA in T cells. HTLV-1 replication is positively regulated by Tax and Rex and negatively regulated by the p30 and HBZ proteins. In the present study, we demonstrate that HTLV-1 encodes another negative regulator of virus expression, the p13 protein. Expressed separately, p13 localizes to the mitochondria, whereas in the presence of Tax, part of it is ubiquitinated, stabilized, and rerouted to the nuclear speckles. The p13 protein directly binds Tax, decreases Tax binding to the CBP/p300 transcriptional coactivator, and, by reducing Tax transcriptional activity, suppresses viral expression. Because Tax stabilizes its own repressor, these findings suggest that HTLV-1 has evolved a complex mechanism to control its own replication. Further, these results highlight the importance of studying the function of the HTLV- 1 viral proteins, not only in isolation, but also in the context of full viral replication. (Blood. 2011;118(6):1549-1559)