An acidic cluster of the cytoplasmic tail of the RD114 virus glycoprotein controls assembly of retroviral envelopes
An acidic cluster of the cytoplasmic tail of the RD114 virus glycoprotein controls assembly of retroviral envelopes
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DOI：
10.1111/j.1600-0854.2007.00581.x
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发表时间：
2007-07-01
期刊：
影响因子：
4.5
通讯作者：
Cosset, Francois-Loic
中科院分区：
文献类型：
--
作者：
Bouard, David;Sandrin, Virginie;Cosset, Francois-Loic
逆转录病毒核心蛋白、Gag和包膜（Env）糖蛋白从不同的细胞区域表达，因此需要相遇以组装感染性颗粒。病毒组分的内在细胞定位特性或它们相互作用的能力决定了感染性颗粒的组装。在这里，我们解决如何Env决定簇和细胞分选蛋白允许来自γ逆转录病毒，小鼠白血病病毒（MLV）和RD 114的Env，旅行到或从晚期内体（LE），这可能代表逆转录病毒在某些细胞中的Env装配位点。MLV Env的单独表达导致其在LE中蓄积，而RD 114 Env需要γ逆转录病毒Gag蛋白的存在。为了区分内在的细胞内Env定位和γ逆转录病毒Gag/Env相互作用在影响Env病毒掺入，我们研究了Env组装在异源慢病毒颗粒上，它们被被动招募。我们发现RD 114 Env胞质尾C端的酸性簇决定了其亚细胞定位和逆行转运。该基序的突变诱导RD 114 Env的晚期内体浓缩，与病毒掺入和感染性的增加相关。相反，MLV Env中功能差的酸性基序的增强导致其晚期内体定位的显著降低，导致具有低Env密度的弱感染性慢病毒颗粒。最后，通过上调与下调其细胞表达，我们表明，磷酸弗林酸性簇分选蛋白1（PACS-1）控制RD 114 Env酸性簇的功能，分配给这个细胞效应器在调制一些逆转录病毒的Env装配的关键作用。
Retroviral core proteins, Gag and envelope (Env) glycoproteins are expressed from distinct cellular areas and therefore need to encounter to assemble infectious particles. The intrinsic cell localisation properties of either viral component or their capacity to mutually interact determines the assembly of infectious particles. Here, we address how Env determinants and cellular sorting proteins allow the Env derived from gamma retroviruses, murine leukemia virus (MLV) and RD114, to travel to or from late endosomes (LE), which may represent the Env assembly site of retroviruses in some cells. The individual expression of MLV Env resulted in its accumulation in LE in contrast to RD114 Env that required the presence of gamma retroviral Gag proteins. To discriminate between intrinsic intracellular Env localisation and gamma retroviral Gag/Env interactions in influencing Env viral incorporation, we studied Env assembly on heterologous lentiviral particles on which they are passively recruited. We found that an acidic cluster present at the C-terminus of the RD114 Env cytoplasmic tail determines its sub-cellular localisation and retrograde transport. Mutation of this motif induced late endosomal concentration of the RD114 Env, correlating with increased viral incorporation and infectivity. Reciprocally, the reinforcement of a poorly functional acidic motif in the MLV Env resulted in a marked decrease of its late endosomal localisation, leading to weakly infectious lentiviral particles with low Env densities. Finally, through upregulation versus downregulation of its cellular expression, we show that phosphofurin acidic-cluster-sorting protein 1 (PACS-1) controls the function of the RD114 Env acidic cluster, assigning to this cellular effector a crucial role in modulation of Env assembly of some retroviruses.