Vpu and BST2: Still Not There Yet?
Vpu and BST2: Still Not There Yet?
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DOI：
10.3389/fmicb.2012.00131
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发表时间：
2012
影响因子：
5.2
通讯作者：
Koyanagi Y
中科院分区：
文献类型：
--
作者：
Sato K;Gee P;Koyanagi Y
广泛的研究已经确定了两种人类细胞蛋白，它们能有效地抑制HIV-1型（HIV-1）的复制，并被广泛接受为“限制性因子”。APOBEC3G被鉴定为一种限制性因子，通过诱导病毒基因组中的G-to-A超突变来减少HIV-1复制，而BST2被鉴定为另一种限制性因子，通过将新生病毒粒子拴在受感染细胞表面来损害新生病毒粒子的释放。为了对抗这些限制因子，HIV-1已经装备了自己的武器：病毒感染因子（Vif）降解APOBEC3G，而病毒蛋白U （Vpu）拮抗BST2。这些发现使我们进一步了解病毒与宿主的相互作用，即病毒因子与宿主限制因子之间的相互作用。在第一种情况下，APOBEC3G和Vif之间的相互作用是明确的：Vif缺陷的HIV-1无法在表达APOBEC3G的细胞中复制。这一发现直接表明APOBEC3G是一种真正的限制性因子，具有抗HIV-1的内在免疫力，而Vif是HIV-1感染的先决条件。换句话说，Vif和APOBEC3G之间的关系已经“成熟”，Vif已经高度进化以克服APOBEC3G。另一方面，尽管BST2极大地削弱了vpu缺陷HIV-1病毒体的释放，但令人困惑的是，vpu缺陷HIV-1仍然能够在表达BST2的细胞中复制。这些发现表明bst2介导的抗HIV-1活性是脆弱的，Vpu对于HIV-1感染是必不可少的。如果是这样，为什么Vpu获得了对抗BST2的潜力？它对HIV-1是否必要或重要？还是Vpu和BST2的关系还“不成熟”？在这篇综述中，我们特别关注Vpu和BST2之间的相互作用。我们讨论了Vpu进化为BST2的有效拮抗剂的可能性，最后提出了Vpu进化为HIV-1人际传播的促进子的假设。自1981年首次报告获得性免疫缺陷综合征患者以来，艾滋病毒-1在世界范围内爆炸性传播，目前已成为一种大流行病。这篇综述提出了一个概念，即当前的HIV-1大流行可能部分归因于Vpu。
Extensive investigations have identified two cellular proteins in humans that potently inhibit HIV type 1 (HIV-1) replication and are widely accepted as “restriction factors.” APOBEC3G was identified as a restriction factor that diminishes HIV-1 replication by inducing G-to-A hypermutation in the viral genome, while BST2 has been identified as another restriction factor that impairs the release of nascent virions by tethering them on the surface of infected cells. To counter these restriction factors, HIV-1 has equipped itself with its own weapons: viral infectivity factor (Vif) degrades APOBEC3G, while viral protein U (Vpu) antagonizes BST2. These findings have allowed us to further our understanding of virus–host interaction, namely, the interplay between viral factors versus host restriction factors. In the first case, the interplay between APOBEC3G and Vif is clear: vif-deficient HIV-1 is incapable of replicating in APOBEC3G-expressing cells. This insight directly indicates that APOBEC3G is a bona fide restriction factor and has intrinsic immunity against HIV-1, and that Vif is a prerequisite for HIV-1 infection. In other words, the relationship between Vif and APOBEC3G has already “matured,” and Vif has highly evolved to overcome APOBEC3G. On the other hand, although BST2 drastically impairs the release of vpu-deficient HIV-1 virions, it is puzzling that vpu-deficient HIV-1 is still able to replicate in BST2-expressing cells. These insights imply that BST2-mediated anti-HIV-1 activity is vulnerable, and that Vpu is dispensable for HIV-1 infection. If so, why has Vpu acquired the counteracting potential against BST2? Was it necessary or important for HIV-1? Or is the relationship between Vpu and BST2 still “immature”? In this review, we particularly focus on the interplay between Vpu and BST2. We discuss the possibility that Vpu has evolved as a potent antagonist against BST2, and finally, propose a hypothesis that Vpu has evolved as a promoter of human-to-human HIV-1 transmission. Since the first report of acquired immunodeficiency syndrome patients in 1981, HIV-1 has spread explosively worldwide and is currently a pandemic. This review proposes a concept suggesting that the current HIV-1 pandemic may be partly attributed by Vpu.
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影响因子：
6.7
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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影响因子：
5.4
作者：
Dietrich, Isabelle;McMonagle, Elizabeth L.;Willett, Brian J.
通讯作者：
Willett, Brian J.
DOI：
10.1073/pnas.0307800101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Belshaw, R;Pereira, V;Tristem, M
通讯作者：
Tristem, M