生物谷Bioon.com導(dǎo)讀：艾滋病病毒外層糖分子鏈結(jié)構(gòu)獨(dú)特,艾滋病病毒外層糖分子鏈結(jié)構(gòu)獨(dú)特,。
關(guān)于艾滋病的近期研究成果：
The Lancet：雞尾酒療法有效降低HIV傳播風(fēng)險(xiǎn)
Science：中和HIV的兩種抗體
PLoS Pathog.：發(fā)現(xiàn)可抑制HIV傳播的抑制劑
PNAS：HIV預(yù)治療可能減少耐藥株的數(shù)量
ACS Chem. Biol：預(yù)防HIV傳播的新分子合成
Nature：HIV Tat復(fù)合物的晶體結(jié)構(gòu)
Cell：Tetherin蛋白阻止HIV從細(xì)胞中釋放機(jī)制
Nat. Biotech.：艾滋病基因治療新進(jìn)展
PLoS Comput Biol ：可快速判斷HIV-1感染的電腦程序
Nature：HIV-1整合酶三維結(jié)構(gòu)
近日英國(guó)牛津大學(xué)網(wǎng)站發(fā)布新聞公報(bào)稱,，該校領(lǐng)導(dǎo)的一國(guó)際研究小組研究發(fā)現(xiàn),，艾滋病病毒（HIV）外層包裹的糖分子鏈結(jié)構(gòu)獨(dú)特且十分穩(wěn)定,，這與人體其他細(xì)胞完全不同。研究人員指出,，可利用這個(gè)特點(diǎn)開(kāi)發(fā)新型艾滋病疫苗,，以使人體免疫系統(tǒng)能夠識(shí)別易變的HIV，并對(duì)抗感染,。
來(lái)自英國(guó)牛津大學(xué),、美國(guó)加州斯克里普斯研究所和馬薩諸塞州波士頓Ragon研究所的研究人員組成的國(guó)際研究小組，對(duì)來(lái)自世界不同地區(qū)的HIV進(jìn)行了分析,。他們從各種HIV-1活體病毒樣本中剝離出碳水化合物層（糖衣）,，在對(duì)其化學(xué)結(jié)構(gòu)進(jìn)行分析后發(fā)現(xiàn)，這種糖存在于所有的HIV-1病毒及其進(jìn)化枝中,，其結(jié)構(gòu)是獨(dú)一無(wú)二的,，與人體細(xì)胞中的其他糖形式完全不同。
研究人員還發(fā)現(xiàn),，目前開(kāi)發(fā)中的艾滋病疫苗的糖結(jié)構(gòu)與HIV中的糖結(jié)構(gòu)并不一樣,，因此可能導(dǎo)致這些疫苗無(wú)法完全模擬HIV。
領(lǐng)導(dǎo)此項(xiàng)研究的英國(guó)牛津大學(xué)克里斯·斯坎倫博士指出,，病毒外層包裹的緊密糖衣被稱做“碳水化合物偽裝層”,，因?yàn)檫@個(gè)糖鏈看起來(lái)和人體細(xì)胞外層糖鏈一樣，一般情況下很難被免疫系統(tǒng)識(shí)別,。而新發(fā)現(xiàn)表明,，HIV的這種偽裝是有缺陷的，HIV上糖的特殊性或許提供了攻擊病毒的機(jī)會(huì),。通過(guò)疫苗配方中設(shè)置的危險(xiǎn)信號(hào),，可以迫使免疫系統(tǒng)注意這種特殊的糖結(jié)構(gòu)，從而識(shí)別HIV,。斯坎倫博士稱,，一些癌癥疫苗的開(kāi)發(fā)就是利用了這種方法。
斯坎倫博士指出,，HIV極其易變,，一個(gè)HIV感染者體內(nèi)病毒在一天之內(nèi)的變化，比整個(gè)英國(guó)一個(gè)流感季節(jié)流感病毒的變化還要多,。這種病毒易變性對(duì)于開(kāi)發(fā)艾滋病疫苗來(lái)說(shuō)是個(gè)不小的挑戰(zhàn),。而發(fā)現(xiàn)HIV外層糖鏈的特殊性，將有助于找到一種開(kāi)發(fā)艾滋病疫苗的新方法,。(生物谷Bioon.com)
>>>借著上海世博會(huì)的良好契機(jī),，"第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國(guó)際研討會(huì)"將于2010年10月12日在中國(guó)上海盛大開(kāi)幕，這將為廣大活躍在腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)第一線的科研工作者提供一個(gè)互動(dòng)交流的平臺(tái),。
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生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1006498107
Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens
Katie J. Dooresa,b,1, Camille Bonomellic,1, David J. Harveyc, Snezana Vasiljevicc, Raymond A. Dwekc, Dennis R. Burtona,b, Max Crispinc, and Christopher N. Scanlanc,2
aDepartment of Immunology and Microbial Science and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037;
bThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02114; and
cOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
The envelope spike of HIV is one of the most highly N-glycosylated structures found in nature. However, despite extensive research revealing essential functional roles in infection and immune evasion, the chemical structures of the glycans on the native viral envelope glycoprotein gp120—as opposed to recombinantly generated gp120—have not been described. Here, we report on the identity of the N-linked glycans from primary isolates of HIV-1 (clades A, B, and C) and from the simian immunodeficiency virus. MS analysis reveals a remarkably simple and highly conserved virus-specific glycan profile almost entirely devoid of medial Golgi-mediated processing. In stark contrast to recombinant gp120, which shows extensive exposure to cellular glycosylation enzymes (>70% complex type glycans), the native envelope shows barely detectable processing beyond the biosynthetic intermediate Man5GlcNAc2 (<2% complex type glycans). This oligomannose (Man5–9GlcNAc2) profile is conserved across primary isolates and geographically divergent clades but is not reflected in the current generation of gp120 antigens used for vaccine trials. In the context of vaccine design, we also note that Manα1→2Man-terminating glycans (Man6–9GlcNAc2) of the type recognized by the broadly neutralizing anti-HIV antibody 2G12 are 3-fold more abundant on the native envelope than on the recombinant monomer and are also found on isolates not neutralized by 2G12. The Manα1→2Man residues of gp120 therefore provide a vaccine target that is physically larger and antigenically more conserved than the 2G12 epitope itself. This study revises and extends our understanding of the glycan shield of HIV with implications for AIDS vaccine design.
