生物谷報道：盡管我們知道艾滋病病毒必須要“劫持”人類的蛋白質(zhì)才能對人造成損傷，但我們對病毒所要作用的目標(biāo)一直知之甚少,。在本周四（1月10日）的Science Express,，哈佛大學(xué)的研究人員公布了大量被艾滋病病毒相關(guān)的蛋白質(zhì)，因而朝尋找新艾滋病藥物的征途上邁出了重要的一步,。
HIV表面上看起來是一個簡單的病毒,，僅僅有9個基因,。但它們有辦法彌補(bǔ)自身的過于簡單結(jié)構(gòu),，能夠以“兇殘”而復(fù)雜的方法利用宿主的機(jī)器來增殖并破壞宿主,。
全世界的各個實驗室為我們深入了解HIV的生命周期做了許多杰出的工作。在過去的20年時間里,，人們鑒定了數(shù)十個HIV增殖所必需的人類蛋白質(zhì)或作用因子。HIV所利用的蛋白被稱為HIV依賴因子,，目前已經(jīng)發(fā)現(xiàn)了36種,。基于前人的工作,，這項新的研究發(fā)現(xiàn)了273個HIV可能作用的目標(biāo),，其中絕大部分都是第一次被發(fā)現(xiàn)與HIV有關(guān),。
該項研究由波士頓的布瑞根婦女醫(yī)院（Brigham and Women's Hospital）Stephen Elledge領(lǐng)導(dǎo),。他的研究小組利用RNAi技術(shù)在體外逐個干擾人類數(shù)千個基因的表達(dá),，干擾的同時加入一些HIV,，然后觀察其現(xiàn)象,。如果HIV不能良好生長,，則表明必定是缺少所干擾基因的蛋白質(zhì)產(chǎn)物的緣故,。
要搞清楚每種蛋白在HIV的生命周期中所起的具體作用,，還有很多的研究工作要做,。
目前大多數(shù)艾滋病藥物都是直接作用于艾滋病本身的。在2007年8月,，美國政府批準(zhǔn)首個阻止HIV依賴因子的藥物,，一個叫做CCR5的細(xì)胞通道。現(xiàn)在,，人們希望從這個長長的名單中找出藥物能夠起作用的靶點。
生物谷推薦原始出處：
Published Online January 10, 2008
Science DOI: 10.1126/science.1152725
Submitted on November 7, 2007
Accepted on December 21, 2007
Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen
Abraham L. Brass 1, Derek M. Dykxhoorn 2, Yair Benita 3, Nan Yan 2, Alan Engelman 4, Ramnik J. Xavier 5, Judy Lieberman 2, Stephen J. Elledge 6*
1 Department of Genetics, Center for Genetics and Genomics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
2 Immune Disease Institute and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
3 Center for Computational and Integrative Biology, Harvard Medical School, Boston, MA 02114, USA.
4 Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
5 Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.; Center for Computational and Integrative Biology, Harvard Medical School, Boston, MA 02114, USA.
6 Department of Genetics, Center for Genetics and Genomics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
* To whom correspondence should be addressed.
Stephen J. Elledge , E-mail: [email protected]
These authors contributed equally to this work.
HIV-1 exploits multiple host proteins during infection. We performed a large-scale siRNA screen to identify host factors required by HIV-1 and identified over 250 HIV-dependency factors (HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral life cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy.
