COPI activity coupled with fatty acid biosynthesis is required for viral replication.
COPI activity coupled with fatty acid biosynthesis is required for viral replication.
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DOI：
10.1371/journal.ppat.0020102
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发表时间：
2006-10
期刊：
影响因子：
6.7
通讯作者：
Perrimon N
中科院分区：
文献类型：
--
作者：
Cherry S;Kunte A;Wang H;Coyne C;Rawson RB;Perrimon N
在不同病毒家族的感染过程中，RNA复制发生在细胞来源的病毒诱导的细胞质膜表面。这一过程是如何调节的，以及需要哪些细胞因子，一直不清楚。此外，宿主-病原体的相互作用，促进这种新的车厢的形成可能是病毒发病机制的关键决定因素，他们的阐明可能会导致新的见解，在感染过程中的囊泡运输事件的协调。在这里，我们表明，在果蝇细胞中，果蝇C病毒重塑高尔基体，并形成一个新的囊泡隔室，在其表面上的病毒RNA复制发生。使用全基因组RNA干扰筛选，我们发现病毒生命周期中的这一步需要至少两个宿主编码的途径：外壳蛋白复合物I（COPI）coatamer和脂肪酸生物合成。我们的研究结果整合，澄清，并扩展了许多关于病毒复制的细胞生物学的观察，使我们能够得出结论，新的细胞膜的形成与这些囊泡从高尔基体的出芽耦合允许这种新的病毒发生细胞器，这是病毒复制所必需的调节生成。此外，由于这些途径在苍蝇和感染相关RNA病毒脊髓灰质炎病毒的人类细胞中也是有限的，因此它们可能代表抗病毒治疗的新靶点。为了成功地入侵宿主并在宿主中复制，病毒劫持了细胞因子。在许多RNA病毒的情况下，包括果蝇小核糖核酸样病毒果蝇C病毒，它们必须在细胞质膜表面进行基因组复制的基本步骤。具体而言，对于小核糖核酸病毒，这些囊泡在感染的细胞中被诱导，并且形成该隔室所需的个体发育和细胞因子尚不清楚。间接证据已经暗示了外壳蛋白复合物I（COPI）、COPII和自噬。在这里，Cherry及其同事使用全基因组RNA干扰筛选方法，使用小核糖核酸样病毒，COPI和脂肪酸生物合成是产生这种细胞内囊泡隔室所需的关键宿主途径，展示了他们的发现。此外，他们表明，COPI的损失，而不是COPII，是保护在成年苍蝇和人类细胞感染相关的小核糖核酸病毒，脊髓灰质炎病毒。这些新的和令人兴奋的发现对小核糖核酸病毒复制和这些途径作为新的抗病毒靶点的潜在用途具有广泛的意义。
During infection by diverse viral families, RNA replication occurs on the surface of virally induced cytoplasmic membranes of cellular origin. How this process is regulated, and which cellular factors are required, has been unclear. Moreover, the host–pathogen interactions that facilitate the formation of this new compartment might represent critical determinants of viral pathogenesis, and their elucidation may lead to novel insights into the coordination of vesicular trafficking events during infection. Here we show that in Drosophila cells, Drosophila C virus remodels the Golgi apparatus and forms a novel vesicular compartment, on the surface of which viral RNA replication takes place. Using genome-wide RNA interference screening, we found that this step in the viral lifecycle requires at least two host encoded pathways: the coat protein complex I (COPI) coatamer and fatty acid biosynthesis. Our results integrate, clarify, and extend numerous observations concerning the cell biology of viral replication, allowing us to conclude that the coupling of new cellular membrane formation with the budding of these vesicles from the Golgi apparatus allows for the regulated generation of this new virogenic organelle, which is essential for viral replication. Additionally, because these pathways are also limiting in flies and in human cells infected with the related RNA virus poliovirus, they may represent novel targets for antiviral therapies. In order to successfully invade and replicate within their hosts, viruses hijack cellular factors. In the case of many RNA viruses, including a Drosophila picorna-like virus Drosophila C virus, they must undergo the essential step of genomic replication on the surface of cytoplasmic membranes. Specifically, for picornaviruses, these vesicles are induced in the infected cell, and the ontogeny and cellular factors required to form this compartment have been unclear. Circumstantial evidence has implicated coat protein complex I (COPI), COPII, and autophagy. Here, Cherry and colleagues present their findings using a genome-wide RNA interference screening approach using a picorna-like virus that COPI and fatty acid biosynthesis are critical host pathways required to generate this intracellular vesicular compartment. Furthermore, they show that loss of COPI, but not COPII, is protective both in adult flies and in human cells infected with the related picornavirus, poliovirus. These novel and exciting findings have broad-scale implications for picornavirus replication and for the potential use of these pathways as novel antiviral targets.
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