Nicot Christophe, Dundr Miroslav, Johnson Julie M, Fullen Jake R, Alonzo Norma, Fukumoto Risaku, Princler Gerald L, Derse David, Misteli Tom, Franchini Genoveffa
Animal Models and Retroviral Vaccines Section, National Cancer Institute, National Institutes of Health, 41/D804, Bethesda, Maryland 20892, USA.
Nat Med. 2004 Feb;10(2):197-201. doi: 10.1038/nm984. Epub 2004 Jan 18.
Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) persists despite a vigorous virus-specific host immune response, and causes adult T-cell leukemia and lymphoma in approximately 2% of infected individuals. Here we report that HTLV-1 has evolved a genetic function to restrict its own replication by a novel post-transcriptional mechanism. The HTLV-1-encoded p30(II) is a nuclear-resident protein that binds to, and retains in the nucleus, the doubly spliced mRNA encoding the Tax and Rex proteins. Because Tex and Rex are positive regulators of viral gene expression, their inhibition by p30(II) reduces virion production. p30(II) inhibits virus expression by reducing Tax and Rex protein expression.
尽管宿主针对1型人类T细胞白血病/淋巴瘤病毒（HTLV-1）存在强烈的病毒特异性免疫反应，但该病毒仍能持续存在，并在约2%的感染者中引发成人T细胞白血病和淋巴瘤。在此，我们报告HTLV-1通过一种新的转录后机制进化出了一种限制自身复制的遗传功能。HTLV-1编码的p30(II)是一种定位于细胞核的蛋白质，它与编码Tax和Rex蛋白的双剪接mRNA结合，并将其保留在细胞核中。由于Tax和Rex是病毒基因表达的正调控因子，p30(II)对它们的抑制作用会减少病毒粒子的产生。p30(II)通过降低Tax和Rex蛋白的表达来抑制病毒表达。
