刊登在近日的國(guó)際雜志Nature上的一篇研究報(bào)告中,,來(lái)自Trinity生物醫(yī)學(xué)研究所的研究者揭示,病毒可以操控人類的免疫系統(tǒng)從而影響免疫效應(yīng),。
這項(xiàng)研究測(cè)試了30種病毒對(duì)于人類細(xì)胞的防御網(wǎng)絡(luò)的效應(yīng),,并且揭示了病毒如何尋找避免免疫系統(tǒng)的方法,最終削減免疫效應(yīng),。研究發(fā)現(xiàn)為研究者開發(fā)出特異的抗病毒療法以及新型藥物提供了思路,。
研究者收集了70種已知的調(diào)節(jié)免疫系統(tǒng)的病毒基因,并且系統(tǒng)性地將這些基因插入到人類細(xì)胞中,,這些基因?qū)?huì)產(chǎn)生30種不同的病毒,,包括痘病毒類、皰疹病毒,、流感病毒和丙肝病毒,。然后研究者使用質(zhì)譜分析法來(lái)分析插入基因所產(chǎn)生的病毒蛋白所作用的人類蛋白質(zhì),運(yùn)用生物信息學(xué)技術(shù)完全分析病毒蛋白和人類蛋白的相互作用,。最終研究者確證了一些新的病毒-人類相互反應(yīng),。
文章中的研究數(shù)據(jù)解釋了病毒可以以大范圍的細(xì)胞過程為靶點(diǎn),而且有些細(xì)胞過程具有抗病毒的作用,,這在以前并沒有報(bào)道過,。既然研究者發(fā)現(xiàn)了病毒攻擊細(xì)胞常見的和特殊的靶位,那么后期研究工作中,,研究者將設(shè)計(jì)出抗病毒療法來(lái)針對(duì)特殊的病毒以及廣譜病毒,。(生物谷Bioon.com)
編譯自:New ways viruses affect human immune response discovered
doi:10.1038/nature11289
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PMID:
Viral immune modulators perturb the human molecular network by common and unique strategies
Andreas Pichlmair, Kumaran Kandasamy, Gualtiero Alvisi, Orla Mulhern, Roberto Sacco, Matthias Habjan, Marco Binder, Adrijana Stefanovic, Carol-Ann Eberle, Adriana Goncalves, Tilmann Bürckstümmer, André C. Müller, Astrid Fauster, Cathleen Holze, Kristina Lindsten, Stephen Goodbourn, Georg Kochs, Friedemann Weber, Ralf Bartenschlager, Andrew G. Bowie, Keiryn L. Bennett, Jacques Colinge & Giulio Superti-Furga
Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms1, 2. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes3, 4. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies5, 6, 7, 8, 9, 10, 11. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.