Nature：科学家成功解析HIV的外壳结构

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<p align="center"><span style="font-family: 楷体_GB2312; font-size: x-small;">病毒蛋白外壳的形状（蓝色/绿色）从不成熟（上图）到成熟（下图）</span></p>
<p align="center"><span style="font-family: 楷体_GB2312; font-size: x-small;">(Credit: ©EMBL/T.Bharat)</span></p>
近日，来自欧洲分子生物学实验室的研究人员首次揭开了HIV病毒外壳的精细结构，相关研究成果刊登在了近日的国际杂志<em>Nature</em>上。反转录病毒由遗传物质和外壳蛋白组成，遗传信息包装于外壳蛋白中，当HIV进入机体免疫细胞之后，便开始复制成很多拷贝。研究者John Briggs表示，HIV新复制产生病毒乃至其成熟所需要的成分均来自于宿主细胞，而且病毒的外壳改变的速度非常之外，出乎了我们的意料。

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成熟和未成熟的病毒外壳都成蜂窝样的六角形单位，用电子扫描以及计算机的方法，研究者试图去寻找构建未成熟病毒外壳的关键蛋白，在成熟病毒的外壳中寻找这种关键蛋白非常困难。

研究发现将为我们设计抗逆转录病毒疗法提供帮助，许多抗逆转录病毒的药物都可以通过封堵酶类来阻止病毒成熟，但是当前并没有批准的药物用于病毒外壳以及锁定特定的病毒酶类。尽管研究中的病毒外壳来源于Mason-Pfizer猴子并且在实验室经过人工修饰，但是病毒非常类似于HIV的天然形态。

研究者后期依然需要进行大量的研究来比较成熟病毒和未成熟病毒之间的结构，这项研究为潜在的以病毒外壳为靶点的药物研发提供了一些思路。

编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/06/120604092852.htm" target="_blank">Shape-Shifting Shell of Retroviruses Detailed</a>

编译者：T.Shen
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<a title="" href="http://dx.doi.org/doi:10.1038/nature11169" target="_blank">doi:10.1038/nature11169</a>
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<br/><strong>Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy </strong><br/>


Tanmay A. M. Bharat, Norman E. Davey, Pavel Ulbrich, James D. Riches, Alex de Marco, Michaela Rumlova, Carsten Sachse, Tomas Ruml &amp; John A. G. Briggs

The assembly of retroviruses such as HIV-1 is driven by oligomerization of their major structural protein, Gag. Gag is a multidomain polyprotein including three conserved folded domains: MA (matrix), CA (capsid) and NC (nucleocapsid)1. Assembly of an infectious virion proceeds in two stages2. In the first stage, Gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to release an enveloped immature virus particle. In the second stage, cleavage of Gag by the viral protease leads to rearrangement of the particle interior, converting the non-infectious immature virus particle into a mature infectious virion. The immature Gag shell acts as the pivotal intermediate in assembly and is a potential target for anti-retroviral drugs both in inhibiting virus assembly and in disrupting virus maturation3. However, detailed structural information on the immature Gag shell has not previously been available. For this reason it is unclear what protein conformations and interfaces mediate the interactions between domains and therefore the assembly of retrovirus particles, and what structural transitions are associated with retrovirus maturation. Here we solve the structure of the immature retroviral Gag shell from Mason–Pfizer monkey virus by combining cryo-electron microscopy and tomography. The 8-Å resolution structure permits the derivation of a pseudo-atomic model of CA in the immature retrovirus, which defines the protein interfaces mediating retrovirus assembly. We show that transition of an immature retrovirus into its mature infectious form involves marked rotations and translations of CA domains, that the roles of the amino-terminal and carboxy-terminal domains of CA in assembling the immature and mature hexameric lattices are exchanged, and that the CA interactions that stabilize the immature and mature viruses are almost completely distinct.

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 <br/>来源：生物谷  

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