Taylor Matthew P, Kirkegaard Karla
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94301, USA.
Autophagy. 2008 Apr;4(3):286-9. doi: 10.4161/auto.5377. Epub 2007 Dec 5.
The RNA replication complexes of small positive-strand RNA viruses such as poliovirus are known to form on the surfaces of membranous vesicles in the cytoplasm of infected mammalian cells. These membranes resemble cellular autophagosomes in their double-membraned morphology, cytoplasmic lumen, lipid-rich composition and the presence of cellular proteins LAMP 1 and LC3. Furthermore, LC3 protein is covalently modified during poliovirus infection in a manner indistinguishable from that observed during bona fide autophagy. This covalent modification can also be induced by the expression of viral protein 2BC in isolation. However, differences between poliovirus-induced vesicles and autophagosomes also exist: the viral-induced membranes are smaller, at 200-400 nm in diameter, and can be induced by the combination of two viral proteins, termed 2BC and 3A. Experimental suppression of expression of proteins in the autophagy pathway was found to reduce viral yield, arguing that this pathway facilitates viral infection, rather than clearing it. We have hypothesized that, in addition to providing membranous surfaces for assembly of viral RNA replication complexes, double-membraned vesicles provide a topological mechanism to deliver cytoplasmic contents, including mature virus, to the extracellular milieu without lysing the cell.
已知脊髓灰质炎病毒等小正链RNA病毒的RNA复制复合体在受感染哺乳动物细胞细胞质中的膜性囊泡表面形成。这些膜在其双膜形态、细胞质内腔、富含脂质的组成以及细胞蛋白LAMP 1和LC3的存在方面类似于细胞自噬体。此外，在脊髓灰质炎病毒感染期间，LC3蛋白以与真正自噬期间观察到的方式无法区分的方式进行共价修饰。这种共价修饰也可以通过单独表达病毒蛋白2BC来诱导。然而，脊髓灰质炎病毒诱导的囊泡与自噬体之间也存在差异：病毒诱导的膜较小，直径为200 - 400纳米，并且可以由两种称为2BC和3A的病毒蛋白组合诱导产生。实验发现，自噬途径中蛋白质表达的抑制会降低病毒产量，这表明该途径促进病毒感染，而不是清除病毒。我们推测，除了为病毒RNA复制复合体的组装提供膜表面外，双膜囊泡还提供了一种拓扑机制，可将包括成熟病毒在内的细胞质内容物递送至细胞外环境而不裂解细胞。
