Nuclear and cytoplasmic effects of human CRM1 on HIV-1 production in rat cells

Nuclear and cytoplasmic effects of human CRM1 on HIV-1 production in rat cells
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DOI:
10.1111/j.1365-2443.2010.01476.x
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发表时间:
2011-02-01
期刊:
影响因子:
2.1
通讯作者:
Shida, Hisatoshi
Shida, Hisatoshi
中科院分区:
生物学4区
文献类型:
--
作者:
Nagai-Fukataki, Mika;Ohashi, Takashi;Shida, Hisatoshi

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人类免疫缺陷病毒1型(HIV-1)调节蛋白Rev通过桥接病毒RNA和输出受体CRM 1介导未剪接gag和单剪接env mRNA的核输出。最近,发现大鼠CRM 1在支持大鼠Rev功能方面不如人CRM 1有效。在这项研究中,为了了解CRM 1在HIV传播中的作用,在大鼠细胞中研究了人类和大鼠CRM 1在HIV-1复制中的功能机制。以p24 Gag蛋白为代表的病毒颗粒的产生通过大鼠细胞中hCRM 1的表达而大大增强;然而,这种效果不仅仅是因为gag mRNA的输出增强。gag mRNA的翻译起始速率没有增加,在hCRM 1存在下,Gag蛋白也不稳定。然而,促进了p55 Gag前体的加工和病毒颗粒的释放。这些结果表明,hCRM 1输出gag mRNA到细胞质,不仅比rCRM 1更有效,而且正确,导致Gag蛋白的有效加工和颗粒形成。
The human immunodeficiency virus type 1 (HIV-1) regulatory protein, Rev, mediates the nuclear export of unspliced gag and singly spliced env mRNAs by bridging viral RNA and the export receptor, CRM1. Recently, rat CRM1 was found to be less efficient than human CRM1 in supporting Rev function in rats. In this study, to understand the role of CRM1 in HIV propagation, the mechanism underlying the function of human and rat CRM1 in HIV-1 replication was investigated in rat cells. The production of viral particles, represented by the p24 Gag protein, was greatly enhanced by hCRM1 expression in rat cells; however, this effect was not simply because of the enhanced export of gag mRNA. The translation initiation rate of gag mRNA was not increased, nor was the Gag protein stabilized in the presence of hCRM1. However, the processing of the p55 Gag precursor and the release of viral particles were facilitated. These results indicated that hCRM1 exports gag mRNA to the cytoplasm, not only more efficiently than rCRM1 but also correctly, leading to efficient processing of Gag proteins and particle formation.