生物谷报道：尽管我们知道艾滋病病毒必须要“劫持”人类的蛋白质才能对人造成损伤，但我们对病毒所要作用的目标一直知之甚少。在本周四（1月10日）的Science Express，哈佛大学的研究人员公布了大量被艾滋病病毒相关的蛋白质，因而朝寻找新艾滋病药物的征途上迈出了重要的一步。
HIV表面上看起来是一个简单的病毒，仅仅有9个基因。但它们有办法弥补自身的过于简单结构，能够以“凶残”而复杂的方法利用宿主的机器来增殖并破坏宿主。
全世界的各个实验室为我们深入了解HIV的生命周期做了许多杰出的工作。在过去的20年时间里，人们鉴定了数十个HIV增殖所必需的人类蛋白质或作用因子。HIV所利用的蛋白被称为HIV依赖因子，目前已经发现了36种。基于前人的工作，这项新的研究发现了273个HIV可能作用的目标，其中绝大部分都是第一次被发现与HIV有关。
该项研究由波士顿的布瑞根妇女医院（Brigham and Women's Hospital）Stephen Elledge领导。他的研究小组利用RNAi技术在体外逐个干扰人类数千个基因的表达，干扰的同时加入一些HIV，然后观察其现象。如果HIV不能良好生长，则表明必定是缺少所干扰基因的蛋白质产物的缘故。
要搞清楚每种蛋白在HIV的生命周期中所起的具体作用，还有很多的研究工作要做。
目前大多数艾滋病药物都是直接作用于艾滋病本身的。在2007年8月，美国政府批准首个阻止HIV依赖因子的药物，一个叫做CCR5的细胞通道。现在，人们希望从这个长长的名单中找出药物能够起作用的靶点。
生物谷推荐原始出处：
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: selledge@genetics.med.harvard.edu
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.
