The human immunodeficiency virus type 1 gag gene encodes an internal ribosome entry site
The human immunodeficiency virus type 1 gag gene encodes an internal ribosome entry site
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DOI：
10.1128/jvi.75.1.181-191.2001
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发表时间：
2001-01-01
影响因子：
5.4
通讯作者：
Siliciano, RF
中科院分区：
文献类型：
--
作者：
Buck, CB;Shen, XF;Siliciano, RF
最近几种逆转录病毒已被证明可以通过内部核糖体进入来促进其gag基因产物的翻译。在这份报告中，我们表明，含有人类免疫缺陷病毒1型（HIV-1）的gag开放阅读框（ORF）的mRNA表现出内部核糖体进入位点（IRES）的活动，可以促进pr556（gag）的翻译起始。值得注意的是，这种IRES活性是由gag ORF本身内的序列驱动的，并且不依赖于天然gag 5 '非翻译区（UTR）。Pr55（gag）翻译的这种帽非依赖性机制可能有助于解释这种蛋白质在面对gag 5 'UTR中发现的扫描核糖体的主要RNA结构障碍时的高水平翻译。这里描述的gag IRES活性还通过在Pr55（gag）衣壳结构域的氨基末端附近发现的内部AUG密码子处的翻译起始来驱动新的40-kDa Gag同种型的翻译。我们的研究结果表明，这种低丰度Gag亚型可能对于培养细胞中HIV-1的野生型复制很重要。HIV-1 gag IRES的活性可能是HIV-1生命周期的一个重要特征，并可作为抗逆转录病毒治疗策略的新靶点。
Several retroviruses have recently been shown to promote translation of their gag gene products by internal ribosome entry. In this report, we show that mRNAs containing the human immunodeficiency virus type 1 (HIV-1) gag open reading frame (ORF) exhibit internal ribosome entry site (IRES) activity that can promote translational initiation of pr556(gag). Remarkably, this IRES activity is driven by sequences within the gag ORF itself and is not dependent on the native gag 5'-untranslated region (UTR). This cap-independent mechanism for Pr55(gag) translation may help explain the high levels of translation of this protein in the face of major RNA structural barriers to scanning ribosomes found in the gag 5' UTR. The gag IRES activity described here also drives translation of a novel 40-kDa Gag isoform through translational initiation at an internal AUG codon found near the amino terminus of the Pr55(gag) capsid domain. Our findings suggest that this low-abundance Gag isoform may be important for wild-type replication of HIV-1 in cultured cells. The activities of the HIV-1 gag IRES may be an important feature of the HIV-l life cycle and could serve as a novel target for antiretroviral therapeutic strategies.