Zhao Wen-Long, Zhang Fan, Feng Du, Wu Ju, Chen Shan, Sui Sen-Fang
Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, PR China.
Biochem Biophys Res Commun. 2009 Jul 3;384(3):347-51. doi: 10.1016/j.bbrc.2009.04.124. Epub 2009 May 3.
Trichosanthin (TCS) is a type I ribosome-inactivating protein that plays dual role of plant toxin and anti-viral peptide. The sorting mechanism of such an exogenous protein is in long pursuit. Here, we examined TCS trafficking in cells expressing the HIV-1 scaffold protein Gag, and we found that TCS preferentially targets the Gag budding sites at plasma membrane or late endosomes depending on cell types. Lipid raft membrane but not the Gag protein mediates the association of TCS with viral components. After Gag budding, TCS is then released in association with the virus-like particles to generate TCS-enriched virions. The resulting TCS-enriched HIV-1 exhibits severely impaired infectivity. Overall, the observations indicate the existence of a unique and elaborate sorting strategy for hijacking HIV-1.
天花粉蛋白(TCS)是一种I型核糖体失活蛋白,具有植物毒素和抗病毒肽的双重作用。这种外源蛋白的分选机制一直是研究的热点。在此,我们研究了TCS在表达HIV-1支架蛋白Gag的细胞中的运输情况,发现TCS根据细胞类型优先靶向质膜或晚期内体上的Gag出芽位点。脂筏膜而非Gag蛋白介导TCS与病毒成分的结合。Gag出芽后,TCS随后与病毒样颗粒一起释放,产生富含TCS的病毒粒子。由此产生的富含TCS的HIV-1表现出严重受损的感染性。总体而言,这些观察结果表明存在一种独特而精细的分选策略来劫持HIV-1。