病毒蛋白外殼的形狀（藍(lán)色/綠色）從不成熟（上圖）到成熟（下圖）
(Credit: ©EMBL/T.Bharat)
近日,，來自歐洲分子生物學(xué)實(shí)驗(yàn)室的研究人員首次揭開了HIV病毒外殼的精細(xì)結(jié)構(gòu),，相關(guān)研究成果刊登在了近日的國際雜志Nature上,。反轉(zhuǎn)錄病毒由遺傳物質(zhì)和外殼蛋白組成,，遺傳信息包裝于外殼蛋白中,，當(dāng)HIV進(jìn)入機(jī)體免疫細(xì)胞之后,，便開始復(fù)制成很多拷貝,。研究者John Briggs表示,，HIV新復(fù)制產(chǎn)生病毒乃至其成熟所需要的成分均來自于宿主細(xì)胞,，而且病毒的外殼改變的速度非常之外，出乎了我們的意料,。
成熟和未成熟的病毒外殼都成蜂窩樣的六角形單位,，用電子掃描以及計算機(jī)的方法,，研究者試圖去尋找構(gòu)建未成熟病毒外殼的關(guān)鍵蛋白，在成熟病毒的外殼中尋找這種關(guān)鍵蛋白非常困難,。
研究發(fā)現(xiàn)將為我們設(shè)計抗逆轉(zhuǎn)錄病毒療法提供幫助,，許多抗逆轉(zhuǎn)錄病毒的藥物都可以通過封堵酶類來阻止病毒成熟，但是當(dāng)前并沒有批準(zhǔn)的藥物用于病毒外殼以及鎖定特定的病毒酶類,。盡管研究中的病毒外殼來源于Mason-Pfizer猴子并且在實(shí)驗(yàn)室經(jīng)過人工修飾,，但是病毒非常類似于HIV的天然形態(tài)。
研究者后期依然需要進(jìn)行大量的研究來比較成熟病毒和未成熟病毒之間的結(jié)構(gòu),，這項(xiàng)研究為潛在的以病毒外殼為靶點(diǎn)的藥物研發(fā)提供了一些思路,。（生物谷Bioon.com）
編譯自：Shape-Shifting Shell of Retroviruses Detailed
編譯者：T.Shen
doi:10.1038/nature11169
PMC:
PMID:
Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy
Tanmay A. M. Bharat, Norman E. Davey, Pavel Ulbrich, James D. Riches, Alex de Marco, Michaela Rumlova, Carsten Sachse, Tomas Ruml & 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.
