Functional studies of an HIV-1 encoded glutathione peroxidase.
Functional studies of an HIV-1 encoded glutathione peroxidase.
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HIV-1 编码的谷胱甘肽过氧化物酶的功能研究。
DOI：
10.1002/biof.5520270109
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Taylor,EthanWill
中科院分区：
文献类型：
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作者：
Zhao,Lijun;Olubajo,Babatunde;Taylor,EthanWill
在与病毒包膜基因重叠的替代阅读框架中，HIV-1已被证明编码截短的谷胱甘肽过氧化物酶（GPx）模块。哺乳动物GPx序列催化核心区的基本活性位点残基在推定的病毒GPx（vGPx，由env-fs基因编码）中是保守的。用HIV-1 env-fsconstruct转染的细胞显示GPx酶活性增加高达100%，并保护其免受线粒体跨膜电位的损失和随后由外源性氧化剂或线粒体活性氧诱导的细胞死亡。观察到完整的vGPx基因在HIV-1感染的长期非进展者中更常见，与艾滋病患者的HIV-1分离株相比。vGPx的抗氧化/抗凋亡保护作用也与观察结果一致，即在精氨酸缺乏时，HIV-1 env-fs序列AAAA阿加（含有潜在的“饥饿”精氨酸密码子阿加）诱导的−1移码增加，这与氧化应激增加有关。在精氨酸限制的条件下，一氧化氮合酶产生超氧化物，超氧化物迅速与NO结合形成过氧亚硝酸盐，过氧亚硝酸盐可导致活化的T细胞发生凋亡。因此，作为对低精氨酸条件的适应性反应的HIV-1 GPx的生物合成可能会延迟氧化剂诱导的凋亡性细胞死亡，为病毒复制提供增强的机会。
In an alternate reading frame overlapping the viral envelope gene, HIV‐1 has been shown to encoded a truncated glutathione peroxidase (GPx) module. Essential active site residues of the catalytic core regions of mammalian GPx sequences are conserved in the putative viral GPx (vGPx, encoded by theenv‐fsgene). Cells transfected with an HIV‐1env‐fsconstruct show up to a 100% increase in GPx enzyme activity, and are protected against the loss of mitochondrial transmembrane potential and subsequent cell death induced by exogenous oxidants or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be more common in HIV‐1‐infected long‐term non‐progressors, as compared to HIV‐1 isolates from patients developing AIDS. An antioxidant/antiapoptotic protective role of the vGPx is also consistent with the observation that −1 frameshifting induced by the HIV‐1env‐fssequence AAAAAGA (which contains a potential “hungry” arginine codon, AGA) increases during arginine deficiency, which has been associated with increased oxidative stress. Under arginine‐limited conditions, nitric oxide synthase generates superoxide, which rapidly combines with NO to form peroxynitrite, which can cause activated T‐cells to undergo apoptosis. Thus, biosynthesis of the HIV‐1 GPx as an adaptive response to low arginine conditions might delay oxidant‐induced apoptotic cell death, providing an enhanced opportunity for viral replication.