Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles
Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles
复制标题
DOI：
10.1128/jvi.74.19.8953-8965.2000
复制
发表时间：
2000-10-01
影响因子：
5.4
通讯作者：
Kirkegaard, K
中科院分区：
文献类型：
--
作者：
Suhy, DA;Giddings, TH;Kirkegaard, K
所有被研究的真核生物的正链RNA病毒都在细胞膜表面组装RNA复制复合体。用脊髓灰质炎病毒和其他小核糖核酸病毒感染哺乳动物细胞，会导致大量重排和水泡形成的膜堆积。在浮力密度梯度中，脊髓灰质炎病毒诱导的膜不包括共裂解、内质网(ER)、溶酶体、线粒体或大多数高尔基体衍生的或内体膜，尽管离子强度的变化影响ER和病毒诱导的囊泡，但不影响其他细胞细胞器。分离表达时，脊髓灰质炎病毒RNA复制复合体的两种病毒蛋白。3A和2C，与内质网共分。然而，在表达2BC(2B和2C蛋白的蛋白分解前体)的细胞中，形成了与脊髓灰质炎病毒感染期间观察到的浮力密度相同的膜。当与2BC共表达时，病毒蛋白3A被定量地掺入这些组分中，形成的膜在超微结构上与脊髓灰质炎病毒感染细胞中的膜相似。这些数据表明，脊髓灰质炎病毒诱导的囊泡来自内质网，通过病毒蛋白2BC和3A的作用，通过一种排除常驻宿主蛋白的机制。脊髓灰质炎病毒诱导的膜的双膜形态、胞浆含量和明显的内质网来源都与这些膜的自噬来源一致。
All positive strand RNA viruses of eukaryotes studied assemble RNA replication complexes on the surfaces of cytoplasmic membranes. Infection of mammalian cells with poliovirus and other picornaviruses results in the accumulation of dramatically rearranged and vesiculated membranes. Poliovirus-induced membranes did not cofractionate,vith endoplasmic reticulum (ER), lysosomes, mitochondria, or the majority of Golgi-derived or endosomal membranes in buoyant density gradients, although changes in ionic strength affected ER and virus-induced vesicles, but not other cellular organelles, similarly. When expressed in isolation, two viral proteins of the poliovirus RNA replication complex. 3A and 2C, cofractionated with ER membranes. However, in cells that expressed 2BC, a proteolytic precursor of the 2B and 2C proteins, membranes identical in buoyant density to those observed during poliovirus infection were formed. When coexpressed with 2BC, viral protein 3A was quantitatively incorporated into these fractions, and the membranes formed were ultrastructurally similar to those in poliovirus-infected cells. These data argue that poliovirus-induced vesicles derive from the ER by the action of viral proteins 2BC and 3A by a mechanism that excludes resident host proteins. The double-membraned morphology, cytosolic content, and apparent ER origin of poliovirus-induced membranes are all consistent with an autophagic origin for these membranes.