Human immunodeficiency virus type 1 Gag polyprotein modulates its own translation
Human immunodeficiency virus type 1 Gag polyprotein modulates its own translation
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DOI：
10.1128/jvi.02596-05
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Lever, Andrew M. L.
中科院分区：
文献类型：
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作者：
Anderson, Emma C.;Lever, Andrew M. L.
人类免疫缺陷病毒1型（HIV-1）的全长病毒RNA既作为病毒结构蛋白Gag和Gag/Pol的mRNA发挥作用，又作为包装在病毒颗粒内的基因组RNA发挥作用。Gag识别的启动基因组折叠的包装信号位于HIV-1 RNA的5'非翻译区（UTR），这也是翻译起始复合物形成的位置。因此，翻译和包装过程之间可能存在竞争。我们研究了Gag调节自身mRNA翻译的能力。Gag对从HIV-1 5' UTR的翻译具有双峰效应，在体外和体内在低浓度下刺激翻译并且在高浓度下抑制翻译。这种抑制作用依赖于Gag通过其核衣壳结构域结合包装信号的能力。刺激活性取决于Gag的基质结构域。这些结果表明，Gag控制着翻译和包装之间的平衡，确保在其基因组扩增之前产生足够的Gag分子来制造病毒颗粒。
The full-length viral RNA of human immunodeficiency virus type 1 (HIV-1) functions both as the mRNA for the viral structural proteins Gag and Gag/Pol and as the genomic RNA packaged within viral particles. The packaging signal which Gag recognizes to initiate genome encapsidation is in the 5' untranslated region (UTR) of the HIV-1 RNA, which is also the location of translation initiation complex formation. Hence, it is likely that there is competition between the translation and packaging processes. We studied the ability of Gag to regulate translation of its own mRNA. Gag had a bimodal effect on translation from the HIV-1 5' UTR, stimulating translation at low concentrations and inhibiting translation at high concentrations in vitro and in vivo. The inhibition was dependent upon the ability of Gag to bind the packaging signal through its nucleocapsid domain. The stimulatory activity was shown to depend on the matrix domain of Gag. These results suggest that Gag controls the equilibrium between translation and packaging, ensuring production of enough molecules of Gag to make viral particles before encapsidating its genome.