Belov George A, Sztul Elizabeth
Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA
J Virol. 2014 Sep 1;88(17):9478-89. doi: 10.1128/JVI.00922-14. Epub 2014 Jun 11.
Viruses are obligatory intracellular parasites and utilize host elements to support key viral processes, including penetration of the plasma membrane, initiation of infection, replication, and suppression of the host's antiviral defenses. In this review, we focus on picornaviruses, a family of positive-strand RNA viruses, and discuss the mechanisms by which these viruses hijack the cellular machinery to form and operate membranous replication complexes. Studies aimed at revealing factors required for the establishment of viral replication structures identified several cellular-membrane-remodeling proteins and led to the development of models in which the virus used a preexisting cellular-membrane-shaping pathway "as is" for generating its replication organelles. However, as more data accumulate, this view is being increasingly questioned, and it is becoming clearer that viruses may utilize cellular factors in ways that are distinct from the normal functions of these proteins in uninfected cells. In addition, the proteincentric view is being supplemented by important new studies showing a previously unappreciated deep remodeling of lipid homeostasis, including extreme changes to phospholipid biosynthesis and cholesterol trafficking. The data on viral modifications of lipid biosynthetic pathways are still rudimentary, but it appears once again that the viruses may rewire existing pathways to generate novel functions. Despite remarkable progress, our understanding of how a handful of viral proteins can completely overrun the multilayered, complex mechanisms that control the membrane organization of a eukaryotic cell remains very limited.
病毒是专性细胞内寄生虫，利用宿主成分来支持关键的病毒过程，包括质膜穿透、感染起始、复制以及宿主抗病毒防御的抑制。在本综述中，我们聚焦于微小核糖核酸病毒，这是一类正链RNA病毒，并讨论这些病毒劫持细胞机制以形成和运作膜性复制复合体的机制。旨在揭示病毒复制结构建立所需因子的研究鉴定出了几种细胞膜重塑蛋白，并促成了一些模型的发展，在这些模型中，病毒“原样”利用预先存在的细胞膜塑形途径来生成其复制细胞器。然而，随着更多数据的积累，这种观点受到越来越多的质疑，并且越来越清楚的是，病毒可能以不同于这些蛋白质在未感染细胞中的正常功能的方式利用细胞因子。此外，以蛋白质为中心的观点正得到重要新研究的补充，这些研究显示了脂质稳态此前未被认识到的深度重塑，包括磷脂生物合成和胆固醇运输的极端变化。关于病毒对脂质生物合成途径修饰的数据仍然很初步，但似乎病毒可能再次重新连接现有途径以产生新功能。尽管取得了显著进展，但我们对少数病毒蛋白如何能完全掌控控制真核细胞膜组织的多层复杂机制的理解仍然非常有限。
